Parkinson’s disease (PD) is a common degenerative disease of central nervous system. Brain mitochondrial dysfunction and structural damage are the important pathogeny of PD. At present, many of Chinese herbal compounds, herbal medicines, and TCM active ingredients are used to prevent and treat PD. The main mechanisms of these medicines are involved in the protection of mitochondrial structure, anti-oxidative stress, anti-calcium dysregulation, mitigation of excitotoxicity, and anti-apoptosis, etc., which also play a comprehensive role through multi-link, multi-level, and multi-target. Through looking up the recent representative literature, the experimental results of Chinese herbal compounds and TCM active ingredients preventing and treating PD through repairing brain mitochondrial structure and function were analyzed and inducted. Many of Chinese herbal compounds and TCM active ingredients were proved to have good effects on PD.

Aim To evaluate the effects of androgra- pholide ( Andro) on suppressing tumor growth and improving mitochondrial function on mouse breast cancer and explore its mechanism.Methods MTT assay was performed to measure the effect of Andro on the growth capacity of mouse breast cancer cell line 4T1.Mice were treated with Andro, then tumor volume measured, organ index calculated and Hematoxylin - eosin ( HE ) stained to detect the inhibitory effect of Andro on tumors.Lactate assay kit was used to detect the lactate level in mouse serum to check glycolysis discrepancy.To illustrate the transformation in oxidative phosphorylation ( OXPHOS) , Acetyl coenzyme A ( Acetyl-CoA ) assay kit was used to ascertain Acetyl-CoA content level , Western blot was used to detect the protein expression of pyruvate dehydrogenase ( PDH) , and ATP assay kit was used to ascertain ATP content level.The mitochondria functions were analyzed: oxygen ( ()2 ) consumption was measured by Clark oxygen electrode, and mitochondrial membrane potential was detected by JC-1 staining.Results Andro could effectively inhibit the proliferation of 4T1 cells and the growth of tumors, and had no significant damage on normal organs.An- clro reduced serum lactic acid content, indicateing that Andro inhibited the process of glycolysis.The expression of PDH, content of acetyl-CoA and ATP content increased with the increase of Andro concentration.It showed that Andro could up-regulate oxidative phosphorylation.In addition, the ()2 consumption and mitochondrial membrane potential increased in 4T1 cells, indicating that Andro could recover mitochondrial function.Conclusions Andro can inhibit the growth of mouse breast cancer, and its mechanism may be related to the inhibition of glycolysis level, restoration of OXPHOS and improvement of mitochondrial function.

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by movement disorders and a loss of dopaminergic (DA) neurons. PD mainly occurs sporadically, but may also result from genetic mutations in several PD-linked genes. Recently, genetic studies with Drosophila mutants, parkin and PINK1, two common PD-associated genes, demonstrated that Parkin acts downstream of PINK1 in maintaining mitochondrial function and integrity. Further studies revealed that PINK1 translocates Parkin to mitochondria and regulates critical mitochondrial remodeling processes. These findings, which suggest that mitochondrial dysfunction is a prominent cause of PD pathogenesis, provide valuable insights which may aid in the development of effective treatments for PD.
Drosophila ; Mitochondria ; Movement Disorders ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are natural by-products of cellular physiological processes involving metabolism of compounds containing oxygen and nitrogen, respectively. Physiological defense mechanisms against ROS/RNS readily convert them into water or urea, but dysregulation of ROS/RNS production damages cells resulting in abnormal conditions such as uncontrolled growth or cell death. ROS/RNS are closely related to the development of a variety of diseases such as cancer, diabetes, neurodegeneration, vascular disease and chronic inflammation. Thus, it has been proposed that the removal of ROS/RNS may prevent or treat oxidative stress-induced diseases. Some antioxidant molecules are synthesized in the body, while others are obtained from food in the diet including fruits, vegetables, meat and even in natural water. In addition to the natural antioxidants, synthetic antioxidants have been modified from natural chemicals so as to increase bioavailability to target organs and increase stability in the air. In developing novel antioxidants for therapeutic use, some factors to consider are: 1) improved efficacy; 2) low side effects (comparatively clear mechanism); 3) competitive price and 4) improved convenience of dosing. In this review, we will discuss the issues mentioned above and the use of antioxidants in clinical application.
Antioxidants ; Biological Availability ; Cell Death ; Defense Mechanisms ; Diet ; Fruit ; Inflammation ; Meat ; Nitrogen ; Oxygen ; Physiological Processes ; Reactive Nitrogen Species ; Reactive Oxygen Species ; Urea ; Vascular Diseases ; Vegetables ; Water

Schwann cells (SCs) in the peripheral nerves myelinate axons during postnatal development to allow saltatory conduction of nerve impulses. Well-organized structures of myelin sheathes are maintained throughout life unless nerves are insulted. After peripheral nerve injury, unidentified signals from injured nerves drive SC dedifferentiation into an immature state. Dedifferentiated SCs participate in axonal regeneration by producing neurotrophic factors and removing degenerating nerve debris. In this review, we focus on the role of mitogen activated protein kinase family proteins (MAP kinases) in SC dedifferentiation. In addition, we will highlight neuregulin 1 and the transcription factor c-jun as upstream and downstream signals for MAP kinases in SC responses to nerve injury.
Action Potentials ; Axons ; Humans ; Myelin Sheath ; Nerve Growth Factors ; Neuregulin-1 ; Peripheral Nerve Injuries ; Peripheral Nerves ; Phosphotransferases ; Plastics* ; Protein Kinases* ; Regeneration ; Schwann Cells ; Transcription Factors

Mitochondria are subcellular organelles composed of two discrete membranes in the cytoplasm of eukaryotic cells. They have long been recognized as the generators of energy for the cell and also have been known to associate with several metabolic pathways that are crucial for cellular function. Mitochondria have their own genome, mitochondrial DNA (mtDNA), that is completely separated and independent from the much larger nuclear genome, and even have their own system for making proteins from the genes in this mtDNA genome. The human mtDNA is a small (~16.5 kb) circular DNA and defects in this genome can cause a wide range of inherited human diseases. Despite of the significant advances in discovering the mtDNA defects, however, there are currently no effective therapies for these clinically devastating diseases due to the lack of technology for introducing specific modifications into the mitochondrial genomes and for generating accurate mtDNA disease models. The ability to engineer the mitochondrial genomes would provide a powerful tool to create mutants with which many crucial experiments can be performed in the basic mammalian mitochondrial genetic studies as well as in the treatment of human mtDNA diseases. In this review we summarize the current approaches associated with the correction of mtDNA mutations in cells and describe our own efforts for introducing engineered mtDNA constructs into the mitochondria of living cells through bacterial conjugation.
Conjugation, Genetic ; Cytoplasm ; DNA ; DNA, Circular ; DNA, Mitochondrial ; Eukaryotic Cells ; Genome ; Genome, Mitochondrial ; Humans ; Membranes ; Metabolic Networks and Pathways ; Mitochondria ; Organelles ; Proteins

Cell Cycle/drug effects* ; Cell Line, Tumor ; Chalcone/pharmacology* ; Humans ; Membrane Potential, Mitochondrial/drug effects* ; Neuronal Outgrowth/drug effects* ; Okadaic Acid/toxicity* ; Reactive Oxygen Species/metabolism* ; Tretinoin/pharmacology* ; tau Proteins/metabolism*

Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-alpha in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.
Axons ; Cell Dedifferentiation ; Chloroquine ; Demyelinating Diseases ; Lysosomes ; Myelin Sheath ; Nerve Growth Factor ; Peripheral Nervous System ; RNA, Messenger ; Schwann Cells ; Tumor Necrosis Factor-alpha ; Wallerian Degeneration

The network pharmacology was used to investigate the material basis and molecular mechanism of Dachengqi Decoction(DCQD) in the treatment of acute pancreatitis(AP). Potential targets of components from DCQD and relevant pathogenic genes of AP were identified through database retrieval. Then, crucial targets were verified with relevant active chemical components via molecular docking. DAVID database was used to explore the functions and pathways involved in the treatment of AP. A total of 108 components were correlated with 28 targets. Molecular docking showed a strong binding ability of key targets and their corresponding compounds. DAVID enrichment analysis showed 438 biological process, 31 molecular functions, 17 cellular components and 96 KEGG pathways. DCQD may achieve its pharmacological effects through anti-inflammatory and anti-oxidative effects, negative regulation of apoptosis and regulation of pancreatic secretion, involving multiple signals, such as IL-17, TNF and NF-κB signaling pathway. In this study, it is the first time to use the method of network pharmacology to reveal the molecular mechanism of DCQD in the treatment of AP by multiple components and multi-signaling pathways, which provides a basis for further biological experiments of AP.
Acute Disease ; Animals ; Molecular Docking Simulation ; Pancreatitis/drug therapy* ; Plant Extracts/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

Movement defects in obesity are associated with peripheral muscle defects, arthritis, and dysfunction of motor control by the brain. Although movement functionality is negatively correlated with obesity, the brain regions and downstream signaling pathways associated with movement defects in obesity are unclear. A dopaminergic neuronal pathway from the substantia nigra (SN) to the striatum is responsible for regulating grip strength and motor initiation through tyrosine hydroxylase (TH) activity-dependent dopamine release. We found that mice fed a high-fat diet exhibited decreased movement in open-field tests and an increase in missteps in a vertical grid test compared with normally fed mice. This motor abnormality was associated with a significant reduction of TH in the SN and striatum. We further found that phosphorylation of c-Jun N-terminal kinase (JNK), which modulates TH expression in the SN and striatum, was decreased under excess-energy conditions. Our findings suggest that high calorie intake impairs motor function through JNK-dependent dysregulation of TH in the SN and striatum.
Animals ; Arthritis ; Brain ; Diet, High-Fat* ; Dopamine ; Dopaminergic Neurons* ; Hand Strength ; JNK Mitogen-Activated Protein Kinases ; Mesencephalon* ; Mice ; Obesity ; Phosphorylation ; Substantia Nigra ; Tyrosine 3-Monooxygenase