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The Mongolian medical silver needles often encounter issues of bending, fracturing, and blunting in clinical applications. Similarly, Mongolian warm needles can cause burns on patients due to inaccurate temperature control. In this study, we developed an Ag85Cu15 alloy specifically for acupuncture needles based on material preparation. By incorporating appropriate amounts of Mn and Ti elements, we were able to enhance the mechanical properties and biocompatibility of the acupuncture needles. Compared to commercially available silver needles, this alloy exhibited a significant increase in microhardness up to 210.2 Hv0.2 and an improved tensile strength of 880.2 MPa. Furthermore, we designed a thermoelectric effect-based temperature measurement model for precise control of the warm needle's temperature, enhancing the therapeutic effectiveness of the treatment.
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ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Mongolian medicine Eerdun Wurile (EW) has remarkable neural recovery effect, and has been playing a key role in the clinical treatment of neurological disorders including ischemic stroke in Inner Mongolia Autonomous Region of China. The preliminary pharmacological studies in animal suggested that EW regulates the expression of trophic factors in brain lesion and may also balance the polarization of activated microglia (Gaowa et al., 2018). AIM OF THE STUDY: The pool of leading bioactive chemicals underlying the therapeutic effects of EW has not been identified. Therefore, the mechanism of action of EW is poorly understood. This study was aimed to identify the major group of compounds that contribute to the inhibition of neuroinflammation during stroke recovery through regulation of microglia polarization. MATERIALS AND METHODS: The extracts of EW in different solvents were evaluated for their inhibitory ability of cytokine (IP-10) expression in LPS stimulated BV2 cells. The most effective extract (of petroleum ether extract) was further separated to 18 fractionations on a semi-preparative HPLC column, which were assess for the IP-10 down-regulation efficiency by RT-qPCR. The potent isolate was further fractionated in 12 fractions, which showed fewer peaks. The fraction 6 from this isolates, which remarkably down-regulates cytokines expression including IP-10, TNFα and IL-1ß, was analyzed on UPLC-qTOF MS. The key chemicals were measured for their cytokine inhibition in BV2 cells and mouse primary microglia. RESULTS: After two consecutive fractionating by preparative HPLC, petroleum ether extraction of EW gave 12 fractions with relatively distinctive chromatograms. A particular fraction (fraction 6) preserved the inhibitory effects on expression of pro-inflammatory cytokines including IP-10, TNFα, IL-1ß and iNOS. The result of UPLC-qTOF MS analysis showed that the fraction contains 21 chemicals including costunolide, alantolactone, myristicin and linolenic acid, which significantly down-regulate the expression of key pro-inflammatory cytokines in LPS stimulated BV2 cells as well as mouse primary microglia. CONCLUSION: Collectively our data suggest that the bioactive chemical pool which is responsible for the therapeutic effects of EW can be extracted in petroleum ether, and fractionated to a relatively small multiple components. Such components include known anti-inflammatory chemicals, which may contribute to the possible microglia polarization in brain lesion during the recovery of ischemic stroke.
Assuntos
Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Medicina Tradicional da Mongólia , Microglia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Linhagem Celular , Regulação para Baixo , Humanos , Inflamação/metabolismo , Medicina Tradicional , Extratos Vegetais/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Eerdun Wurile (EW) is one of the key Mongolian medicines for treatment of neurological and cardiological disorders. EW is ranked most regularly used Mongolian medicine in clinic. Components of EW which mainly originate from natural products are well defined and are unique to Mongolian medicine. AIM OF THE STUDY: Although the recipe of EW contains known neuroactive chemicals originated from plants, its mechanism of action has never been elucidated at molecular level. The objective of the present study is to explore the mechanism of neuroregenerative activity of EW by focusing on the regulation of gene expression in the brain of rat model of stroke. MATERIALS AND METHODS: Rat middle cerebral artery occlusion (MCAO) models were treated with EW for 15 days. Then, total RNAs from the cerebral cortex of rat MCAO models treated with either EW or control (saline) were extracted and analyzed by transcriptome sequencing. Differentially expressed genes were analyzed for their functions during the recovery of ischemic stroke. The expression level of significantly differentially expressed genes such as growth factors, microglia markers and secretive enzymes in the lesion was further validated by RT-qPCR and immunohistochemistry. RESULTS: Previously identified neuroactive compounds, such as geniposide (Yu et al., 2009), myristicin (Shin et al., 1988), costunolide (Okugawa et al., 1996), toosendanin (Shi and Chen, 1999) were detected in EW formulation. Bederson scale indicated that the treatment of rat MCAO models with EW showed significantly lowered neurological deficits (pâ¯<â¯0.01). The regional cerebral blood circulation was also remarkably higher in rat MCAO models treated with EW compared to the control group. A total of 186 genes were upregulated in the lesion of rat MCAO models treated with EW compared to control group. Among them, growth factors such as Igf1 (pâ¯<â¯0.05), Igf2 (pâ¯<â¯0.01), Grn (pâ¯<â¯0.01) were significantly upregulated in brain after treatment of rat MCAO models with EW. Meanwhile, greatly enhanced expression of microglia markers, as well as complementary components and secretive proteases were also detected. CONCLUSION: Our data collectively indicated that EW enhances expression of growth factors including Igf1 and Igf2 in neurons and microglia, and may stimulate microglia polarization in the brain. The consequences of such activity include stimulation of neuron growth, hydrolysis and clearance of cell debris at the lesion, as well as the angiogenesis.
Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Exsudatos de Plantas/uso terapêutico , Animais , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Circulação Cerebrovascular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Masculino , Medicina Tradicional da Mongólia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/análise , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Exsudatos de Plantas/análise , Ratos WistarRESUMO
OBJECTIVE: To study the analgesic, antipyretic and anti-inflammatory effect of Bailian Caogen granule. METHOD: The antipyretic effects of Bailian Caogen granule was evaluated in rabbit fever model induced by peptone. The analgesic effect of the drug was studied with pain model of mice induced by acetic acid and hot plate, The severity of oedema in inflamed animal was observed to study the anti-inflammatory effects of Bailian Caogen granule. RESULT: Bailian Caogen granule could obviously inhibit the fever of rabbits. The number of writhing induced by acetic acid was reduced and the pain threshold of mice was increased by Bailian Caogen granule. Bailian Caogen granule also had anti-inflammatory activity against xylene-induced mouse ear swelling and carrageenin-induced rat paw edema. CONCLUSION: Bailian Caogen granule has significant analgesic, antipyretic and anti-inflammatory activities.