dynamic-continuous-blood-extraction-from-rat-heart-via-noninvasive

Dynamic Continuous Blood Extraction from Rat Heart <em>via</em> Noninvasive Microdialysis Technique

Dynamic analysis of blood components is of great importance in understanding cardiovascular diseases and their related diseases, such as myocardial ...

Chengdu University of Traditional Chinese Medicine

Ershi-wei Chenxiang pills (ECP) or Aga Nixiu wan (ཨ་གར་ཉི་ཤུ།), composed of 20 Tibetan medicines, has the effect of promoting blood circulation to remove blood stasis. As a common and frequent prescription used by traditional Tibetan medicine in clinical treatment of Longzhibu disease (cerebral ischemia sequelae), it has a significant effect. However, its anti-cerebral ischemia mechanism is still unclear.

Longzhibu disease and its therapeutic effects by traditional Tibetan medicine: Ershi-wei Chenxiang pills.

Mammalian mitochondrial permeability transition pore (MPTP), across the inner and outer membranes of mitochondria, is a nonspecific channel for signal transduction or material transfer between mitochondrial matrix and cytoplasm such as maintenance of Ca homeostasis, regulation of oxidative stress signals, and protein translocation evoked by some of stimuli. Continuous MPTP opening has been proved to stimulate neuronal apoptosis in ischemic stroke. Meanwhile, inhibition of MPTP overopening-induced apoptosis has shown excellent efficacy in the treatment of ischemic stroke. Among of which, the potential molecular mechanisms of drug therapy for stroke has also been gradually revealed by researchers. The characteristics of multi-components or multi-targets for ethnic drugs also provide the possibility to treat stroke from the perspective of mitochondrial MPTP. The advantages mentioned above make it necessary for us to explore and clarify the new perspective of ethnic medicine in treating stroke and to determine the specific molecular mechanisms through advanced technologies as much as possible. In this review, we attempt to uncover the relationship between abnormal MPTP opening and neuronal apoptosis in ischemic stroke. We further summarized currently authorized drugs, ethnic medicine prescriptions, herbs, and identified monomer compounds for inhibition of MPTP overopening-induced ischemic neuron apoptosis. Finally, we strive to provide a new perspective and enlightenment for ethnic medicine in the prevention and treatment of stroke by inhibition of MPTP overopening-induced neuronal apoptosis.

Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition.

This study was first and systematically conducted to evaluate the hypoxia response of the brain, heart, lung, liver, and kidney of mice exposed to an animal hypobaric chamber. First, we examined the pathological damage of the above tissues by Hematoxylin & eosin (H&E) staining. Secondly, biochemical assays were used to detect oxidative stress indicators such as superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG). Finally, the hypoxia compensation mechanism of tissues was evaluated by expression levels of hypoxia-inducible factor 1 alpha (HIF-1α), erythropoietin (EPO), and vascular endothelial growth factor (VEGF). During the experiment, the mice lost weight gradually on the first 3 days, and then, the weight loss tended to remain stable, and feed consumption showed the inverse trend. H&E staining results showed that there were sparse and atrophic neurons and dissolved chromatin in the hypoxia group. And hyperemia occurred in the myocardium, lung, liver, and kidney. Meanwhile, hypoxia stimulated the enlargement of myocardial space, the infiltration of inflammatory cells in lung tissue, the swelling of epithelial cells in hepatic lobules and renal tubules, and the separation of basal cells. Moreover, hypoxia markedly inhibited the activity of SOD and GSH and exacerbated the levels of MDA and GSSG in the serum and five organs. In addition, hypoxia induced the expression of HIF-1α, EPO, and VEGF in five organs. These results suggest hypoxia leads to oxidative damage and compensation mechanism of the brain, heart, lung, liver, and kidney in varying degrees of mice.

The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia.

Gallic acid (GA), also known as 3,4,5-trihydroxybenzoic acid, is a natural secondary metabolite and widely isolated from various fruits, plants and nuts. In recent years, GA has received increasing attention for its powerful anti-inflammatory properties. The purpose of this review is to clearly illuminate the pharmacological activities and related molecular mechanisms of GA in inflammatory diseases. After consulting a large number of literatures, we made a comprehensive exposition on the chemical characteristics, plant origins, pharmacokinetics and toxicity of GA, especially its pharmacological activities and mechanisms of action. Although the plant source of GA is very rich, its lower extraction rate limits the application of GA in development. It is worth mentioning that GA can not only be separated from many plants, but also be produced in large quantities through biological and chemical synthesis. According to pharmacokinetic studies, the absorption and elimination of GA after oral administration are fast, while the structural optimization or dosage form adjustment of GA is beneficial to increase its bioavailability. Promisingly, toxicity studies have shown that GA scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials. The results show that the anti-inflammatory mechanisms of GA mainly involved MAPK and NF-κB signaling pathways. It thus weakens the inflammatory response by reducing the release of inflammatory cytokines, chemokines, adhesion molecule and cell infiltration. Due to its excellent pharmacological activities, GA is expected to be a potential candidate for the treatment of various inflammation-related diseases. This paper will provide theoretical basis for the clinical application of GA and guide the future research and medicinal development of GA.

Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases.

Duoxuekang (DXK, ཁྲག་འཕེལ་བདེ་བྱེད།) is a clinical experience prescription of CuoRu-Cailang, a famous Tibetan medicine master, which has effective advantages in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, its underlying mechanisms remain unclear.

Tibetan medicine Duoxuekang ameliorates hypobaric hypoxia-induced brain injury in mice by restoration of cerebrovascular function.

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment.

Imaging in the second near-infrared II (NIR-II) window, a kind of biomedical imaging technology with characteristics of high sensitivity, high resolution, and real-time imaging, is commonly used in the diagnosis of brain diseases. Compared with the conventional visible light (400-750 nm) and NIR-I (750-900 nm) imaging, the NIR-II has a longer wavelength of 1000-1700 nm. Notably, the superiorities of NIR-II can minimize the light scattering and autofluorescence of biological tissue with the depth of brain tissue penetration up to 7.4 mm. Herein, we summarized the main principles of NIR-II in animal models of traumatic brain injury, cerebrovascular visualization, brain tumor, inflammation, and stroke. Simultaneously, we encapsulated the  process of NIR-II probes and their  and  toxic effects. We further dissected its limitations and following optimization measures.

Second near-infrared (NIR-II) imaging: a novel diagnostic technique for brain diseases.

Cantleyoside (CA) is a kind of iridoid glycosides in Pterocephalus hookeri (C. B. Clarke) Höeck. The purpose of this study was to investigate the effects of CA on human rheumatoid arthritis fibroblast synovial cells (HFLS-RA).

The enhanced mitochondrial dysfunction by cantleyoside confines inflammatory response and promotes apoptosis of human HFLS-RA cell line via AMPK/Sirt 1/NF-κB pathway activation.

Rhodiola crenulata is clinically used to combat hypobaric hypoxia brain injury at high altitude with the function of invigorating Qi and promoting blood circulation in Tibetan medicine. Salidroside (Sal), an active compound identified from Rhodiola species, has been shown to exert neuroprotective effects against hypoxic brain injury. However, its mitochondrial protective mechanisms remain largely unknown.

Salidroside, a phenyl ethanol glycoside from Rhodiola crenulata, orchestrates hypoxic mitochondrial dynamics homeostasis by stimulating Sirt1/p53/Drp1 signaling.

Article	Year
Longzhibu disease and its therapeutic effects by traditional Tibetan medicine: Ershi-wei Chenxiang pills. Journal of ethnopharmacology\| PubMed ID: 31775011	2020
Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition. Frontiers in pharmacology\| PubMed ID: 32269527	2020
The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia. Cell stress & chaperones\| PubMed ID: 32430880	2020
Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 33212373	2021
Tibetan medicine Duoxuekang ameliorates hypobaric hypoxia-induced brain injury in mice by restoration of cerebrovascular function. Journal of ethnopharmacology\| PubMed ID: 33246120	2021
Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment. Purinergic signalling\| PubMed ID: 33751327	2021
Second near-infrared (NIR-II) imaging: a novel diagnostic technique for brain diseases. Reviews in the neurosciences\| PubMed ID: 34551223	2021
The enhanced mitochondrial dysfunction by cantleyoside confines inflammatory response and promotes apoptosis of human HFLS-RA cell line via AMPK/Sirt 1/NF-κB pathway activation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 35364376	2022
Salidroside, a phenyl ethanol glycoside from Rhodiola crenulata, orchestrates hypoxic mitochondrial dynamics homeostasis by stimulating Sirt1/p53/Drp1 signaling. Journal of ethnopharmacology\| PubMed ID: 35439546	2022

Jinrong Bai

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