RESUMEN
Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.
Asunto(s)
Berberina , Diabetes Mellitus Tipo 2 , Enfermedades Mitocondriales , Ratones , Animales , Berberina/farmacología , Berberina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/metabolismo , Péptido 1 Similar al Glucagón/farmacología , Péptido 1 Similar al Glucagón/uso terapéutico , Glucosa , Obesidad/metabolismo , Estrés Oxidativo , Enfermedades Mitocondriales/tratamiento farmacológicoRESUMEN
To further investigate the application of positron emission tomography (PET) technology in acupuncture research field, with "PET" and "acupuncture" as keywords, the related literature published from 1997 to 2018 was searched in PubMed, CNKI and WANFANG database; then the literature was classified and analyzed. The results showed that in clinical and experimental studies, whether in physiological or pathological conditions, PET technology has verified the specificity of acupoints, bidirectional regulation of acupoints, and the clinical effect of qi-arrival from the level of brain functional activity. It has deeply revealed the central mechanism underlying that acupuncture has multi-target, multi-channel and multi-level overall effects. The purpose of this study is to provide objective scientific basis for acupuncture research, and then potentially guide the clinical practice.
Asunto(s)
Terapia por Acupuntura , Puntos de Acupuntura , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: To observe the effect of twirling-reducing needling on changes of profile of differentially-expressed genes in the hypothalamus in rats with stress-induced prehypertension (SI-PHT), so as to explore its mechanism under-lying improvement of prehypertension. METHODS: Wistar male rats were randomly divided into blank control group (n=12), model group (n=12) and acupuncture group (n=10). The SI-PHT model was established by planta-electric-shock stimulation (30 V, 5 s) plus noise stimulation (80-100 db, 50 ms), twice daily, continuously for 11 days. Manual acupuncture stimulation (twirling-reducing needling) was applied to bilateral "Taichong" (LR 3) and "Quchi" (LI 11) for about 1 min (60 cycles/min), followed by retaining the needles for 20 min during modeling preparation, once daily for 11 days. The systolic blood pressure (SBP) and behavior changes were recorded before intervention and on the 3rd, 5th, 7th, 9th and 11th day during modeling. The expression (Fold change,|FC| ≥ 1.5) profile of genes in the hypothalamus was analyzed using Affymetrix GeneChip Rat Gene 2.0 ST Array, followed by analyzing the differentially-expressed genes involving the related biological process,molecular function, and signaling pathways by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), separately. RESULTS: After modeling, the systolic pressure levels were remarkably increased from the 3rd day to the 11th day in both model and acupuncture groups relatively to their respective baseline levels (P<0.01), and were significantly lower in the acupuncture group than in the model group (P<0.01) from the 5th day to the 11th day. Meanwhile, 93 genes were up-regulated and 153 down-regulated in the model group relative to the control group (P<0.05,|FC| ≥ 1.5), while in comparison with the model group, 59 genes were up-regulated and 86 down-regulated in the acupuncture group (P<0.05,|FC| ≥ 1.5). The expression levels of the 40 differen-tially-expressed genes (24 up-regulated and 16 down-regulated) in the model group were evidently reversed after acupuncture stimulation (P<0.05,|FC| ≥ 1.5). After acupuncture stimulation, the expression of acyl-CoA synthetase medium-chain family member 3 (Acsm 3) gene was down-regulated, and chorionic gonadotropin-alpha (Cgα), crystal (Cry) αB and thyroid stimulating hormone beta (Tshß) genes and the autoimmune thyroid disease (AITD) pathway were up-regulated (P<0.05,|FC| ≥ 1.5), suggesting an involvement of fatty acid biosynthetic processing, G-protein coupled receptor protein signaling, and hormone activity, etc. in acupuncture-induced blood-pressure lowering. CONCLUSIONS: Twirling-reducing needling of acupuncture can lower blood pressure in prehypertension rats, which may be related to its effects in regulating expression of Acsm 3, Cgα, CryαB, Tshß genes and in activating AITD pathway.