RESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Autofagia , Caenorhabditis elegans , Dendrobium , Modelos Animais de Doenças , Extratos Vegetais , Proteostase , Animais , Caenorhabditis elegans/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Dendrobium/química , Proteostase/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Extratos Vegetais/farmacologia , Animais Geneticamente Modificados , Proteínas tau/metabolismo , Fenóis/farmacologia , Fenóis/isolamento & purificação , Flavanonas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Polygonum multiflorum Thunb (PMT), as a traditional Chinese herbal medicine, has been widely used in the prevention and treatment of aging-related diseases, including Alzheimer's disease, Parkinson's disease, hyperlipidemia, atherosclerosis and inflammation. However, the effect of PMT on the lifespan and its molecular mechanisms are still unclear. Here we found that 60% ethanol refined fraction (PMT-E) of Polygonum multiflorum Thunb at 50 µg mL-1, which contained two main bioactive compounds, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-ß-D-glucoside (EG), could significantly increase the mean lifespan by 19.82%, delay the age-related decline of phenotypes, enhance stress resistance and reduce ROS accumulation in Caenorhabditis elegans. Moreover, we also found that the mitochondrial membrane potential (ΔΨ) and ATP content of worms treated with 50 µg mL-1 PMT-E were obviously improved. Further mechanistic studies revealed that DAF-16, SIR-2.1 and SKN-1 transcription factors were required for PMT-E-mediated lifespan extension. Finally, we found that PMT-E could significantly inhibit the toxicity induced by ß-amyloid (Aß) in Aß transgenic worms. Altogether, these findings laid the foundation for the use of Polygonum multiflorum Thunb to treat aging and age-related diseases.
Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fallopia multiflora , Longevidade/efeitos dos fármacos , Envelhecimento , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Quimiotaxia , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Mitocôndrias/metabolismo , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sirtuínas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Coix seed oil (CSO) has many beneficial effects, but there is limited research on its influence on the processes and mechanisms related to senescence. Here, we used Caenorhabditis elegans as an in vivo model to investigate CSO's bioeffects on longevity. CSO (1 mg/mL) significantly extended the mean lifespan of C. elegans by over 22.79% and markedly improved stress resistance. Gene-specific mutant studies showed that the CSO-mediated increase in life expectancy was dependent on mev-1, hsf-1 and daf-16, but not daf-2. Furthermore, CSO significantly upregulated stress-inducible genes, including daf-16 and its downstream genes (sod-3, hsp-16.2 and gst-4). In addition, four major fatty acids, linoleic, oleic, palmitic and stearic, played leading roles in C. elegans' extended lifespan. Thus, CSO increased the life expectancy of, and enhanced the stress resistance in, C. elegans mainly through daf-16 and its downstream genes, but not through the insulin/insulin-like growth factor 1 signaling pathway.
Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Coix , Longevidade/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Sementes , Estresse Fisiológico/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Coix/química , Citocromos b/genética , Citocromos b/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Óleos de Plantas/isolamento & purificação , Sementes/química , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Acorus tatarinowii Schott [Shi Chang Pu in Chinese (SCP)] is a traditional Chinese medicine frequently used in the clinical treatment of dementia, amnesia, epilepsy, and other mental disorders. Previous studies have shown the potential efficacy of SCP against Alzheimer's disease (AD). Nevertheless, the active constituents and the modes of action of SCP in AD treatment have not been fully elucidated. PURPOSE: The aim of this study was to investigate the protective effects of SCP on abnormal proteins and clarify its molecular mechanisms in the treatment of AD by using a Caenorhabditis elegans (C. elegans) model. METHODS: This study experimentally assessed the effect of SCP-Oil in CL4176 strains expressing human Aß in muscle cells and CL2355 strains expressing human Aß in pan-neurons. Western blotting, qRT-PCR, and fluorescence detection were performed to determine the oxidative stress and signaling pathways affected by SCP-Oil in nematodes. RESULTS: SCP-Oil could significantly reduce the deposition of misfolded Aß and polyQ proteins and improved serotonin sensitivity and olfactory learning skill in worms. The analysis of pharmacological action mechanism of SCP-Oil showed that its maintaining protein homeostasis is dependent on the autophagy pathway regulated partly by hsf-1 and sir-2.1 genes. CONCLUSION: Our results provide new insights to develop treatment strategy for AD by targeting autophagy, and SCP-Oil could be an alternative drug for anti-AD.
Assuntos
Acorus/metabolismo , Precursor de Proteína beta-Amiloide/biossíntese , Precursor de Proteína beta-Amiloide/toxicidade , Autofagia/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Quimiotaxia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Homeostase , Peptídeos/química , Dobramento de Proteína , Transdução de Sinais , Especificidade da EspécieRESUMO
A novel tetralignan, tatarinan T (1) with the rare C8-C7' linkage pattern, along with a known monolignan (2) were isolated from the roots of Acorus tatarinowii Schott. Their chemical structures were elucidated on the basis of NMR and X-ray diffraction analysis. We evaluated the protective effects of two rare lignans against ß-amyloid toxicity by using CL4176 transgenic C. elegans model for the first time, and found that they significantly delayed paralysis of worms at the concentration of 100 µM. Compound 2 exhibited the more potential protective effect against ß-amyloid toxicity, its value of PT50 extended up to 62.3% at 100 µM compared with control, especially, it still has 30.8% extension at 10 µM.
Assuntos
Acorus/química , Caenorhabditis elegans/efeitos dos fármacos , Lignanas/farmacologia , Raízes de Plantas/química , Peptídeos beta-Amiloides/toxicidade , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Medicamentos de Ervas Chinesas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
Obesity is a serious medical problem worldwide. As a holistic therapy, traditional Chinese medicine (TCM) may have a potential in obesity management. In this controlled trial, we evaluated the safety and effectiveness of xin-ju-xiao-gao-fang (XJXGF), a TCM herbal formulation, in 140 obese subjects over a 24-week period. The XJXGF formula mainly consists of rhubarb, coptis, semen cassia, and citrus aurantium. Subjects with body mass index (BMI) 28-40 kg/m(2) were recruited at 5 centers in China. We assessed the changes in subjects' body weight, its related parameters, and the reduction of insulin resistance (IR) after administration of XJXGF formula or low-dose XJXGF (10% of the XJXGF formula, as control). After 24-week treatment, among participants in the XJXGF formula group and low-dose XJXGF group, the mean ± SE changes in the body weight were -3.58 ± 0.48 and -1.91 ± 0.38 kg, respectively (p < 0.01). The changes in the IR-index of two groups were -2.65 ± 1.04 and -1.58 ± 1.3, respectively (p < 0 .05). There were no serious adverse events reported during the 24-week trial. Participants reported 7 minor adverse events, 4 in the XJXGF formula group and 3 in the low-dose XJXGF group (p = 0.578). Future studies are needed to investigate the clinical utility of this TCM formulation in the treatment of obese subjects.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Obesidade/tratamento farmacológico , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal , Cassia , Citrus , Coptis , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Peptídeos Cíclicos , Estudos Prospectivos , Rheum , Fatores de Tempo , Resultado do Tratamento , Circunferência da Cintura , Adulto JovemRESUMO
Chinese Pharmacopoeia I (2010 edition) covers dosage and usage of traditional Chinese medicinal herbs and decoction pieces, and provides dosage ranges of most of decoction pieces. By using the descriptive statistical method, the article discusses the distribution of maximum dosage, minimum dosage and dosage range of decoction pieces set forth in Chinese Pharmacopoeia, and compares toxic drugs and non-toxic drugs. Altogether 617 drugs are included into the study. Except for 16 decoction pieces whose dosages are not clear, all of the remaining decoction pieces are covered by Chinese Pharmacopoeia, with the maximum common dosage, minimum common dosage and dosage range of 3, 10 and 6 g. Upon comparison, we discovered that Chinese Pharmacopoeia sets stricter standards for toxic drugs than non-toxic drugs. Compared with dosages in classical prescriptions and actual clinical usages, dosage ranges described in Chinese Pharmacopoeia are much narrower. There is no significant difference between drugs that can be used as foods or healthcare foods and other drugs according to Chinese Pharmacopoeia.
Assuntos
Tratamento Farmacológico/normas , Medicamentos de Ervas Chinesas/farmacologia , Prescrições/normas , Cálculos da Dosagem de Medicamento , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , HumanosRESUMO
Therapeutic interventions in prediabetes are important in the primary prevention of type 2 diabetes (T2D) and its chronic complications. However, little is known about the pharmacogenetic effect of traditional herbs on prediabetes treatment. A total of 194 impaired glucose tolerance (IGT) subjects were treated with traditional hypoglycemic herbs (Tianqi Jiangtang) for 12 months in this study. DNA samples were genotyped for 184 mutations in 34 genes involved in drug metabolism or transportation. Multinomial logistic regression analysis indicated that rs1142345 (A > G) in the thiopurine S-methyltransferase (TPMT) gene was significantly associated with the hypoglycemic effect of the drug (P = 0.001, FDR P = 0.043). The "G" allele frequencies of rs1142345 in the healthy (subjects reverted from IGT to normal glucose tolerance), maintenance (subjects still had IGT), and deterioration (subjects progressed from IGT to T2D) groups were 0.094, 0.214, and 0.542, respectively. Binary logistic regression analysis indicated that rs1142345 was also significantly associated with the hypoglycemic effect of the drug between the healthy and maintenance groups (P = 0.027, OR = 4.828) and between the healthy and deterioration groups (P = 0.001, OR = 7.811). Therefore, rs1142345 was associated with the clinical effect of traditional hypoglycemic herbs. Results also suggested that TPMT was probably involved in the pharmacological mechanisms of T2D.
RESUMO
A prospective multicenter clinical trial was conducted to compare the beneficial effects of a Chinese herbal medicine formula Jiangzhuoqinggan (JZQG) and western antihypertension drug irbesartan. JZQG is mainly composed of rhubarb, coptis, cassia, and uncaria. A total of 240 patients with mild to moderate hypertension were enrolled in the trial. Patients were assigned into two groups after screening: JZQG group and the irbesartan group. After four weeks of treatment, we compared the changes in routine blood pressure, 24 h ambulatory blood pressure, and waist circumference. There was a significant reduction in systolic blood pressure and diastolic blood pressure in the JZQG group (both p < 0.01). There were no significant differences between the reduction of systolic and diastolic blood pressures in the two treatment groups. From the 24 h ambulatory blood pressure measurement, the JZQG group showed a greater reduction in both systolic and diastolic blood pressures (in both daytime and nighttime) than the irbesartan group. Furthermore, there was a significant difference in waist circumference in the JZQG group (1.51 cm reduction; P < 0.05) but not the irbesartan group (0.42 cm). Thus, the JZQG formula may have therapeutic value in patients with both hypertension and metabolic syndrome.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Irbesartana , Masculino , Síndrome Metabólica/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Circunferência da Cintura/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To observe the therapeutic effect of different dosages of Gegen Qin Lian Decoction on type 2 diabetic patients. METHODS: Fifty-four type 2 diabetic patients from low dosage group (20 cases), medium dosage group (19 cases) and high dosage group (15 cases) were treated with different dosage of Gegen Qin Lian Decoction for 12 weeks. Fasting blood-glucose (FBG), postprandial blood sugar (PBG) and Hemoglobin A1c (HbA1c) were determined before and after treatment. RESULTS: With the increase of dosage, the overall effective rate of glycaemic control increased, and FBG, PBG HbA1c decreased. The overall effective rate of blood glucose control of high dosage, medium dosage and low dosage group were 80%, 47%, 30% respectively, and there were significant differences between high dosage group and low dosage group. The decrease of FBG, PBG and HbA1c of high dosage showed significant differences from low dosage too. These data was analyzed by trend chi2 test and covariance analysis. CONCLUSION: The result indicated that different dosage of Gegen Qin Lian Decoction has dose-effect relationship in reducing HbA1c and FBG.