Latest ArticlesCellular energy metabolism disorder caused by dysfunction of nutrient utilization and mitochondrial damage contributes to a variety of diseases, including neurodegenerative diseases, cancer, metabolic diseases, and cardiovascular diseases. Understanding the effects of energy metabolism on diseases will help to improve our knowledge about disease etiology and may serve to develop strategies to delay disease progress. There are many compounds developed for targeting energy metabolism disorders, such as small molecules targeting the 18 kDa transporter (TSPO) for treatment of Alzheimer's disease, glucagon-like peptide-1 analogues for treatment of Parkinson's disease, inhibitors of glucose transporter 1 (GLUT1) and lactate dehydrogenase A for treatment of tumors, the fibroblast growth factors based treatment for type 2 diabetes (T2D), selective ligands of peroxisome proliferator-activated receptor (PPAR)-β/δ for treatment of cardiovascular diseases. We review here the abnormal energy metabolism of common energy metabolism disorder-related diseases, summarize the potential targets that may be used for new drug discovery, and the strategies for alleviating the disease process by improving energy metabolism.
Natural products with diverse structures and significant biological activities were important source of lead compounds, and have played a key role in the innovative drug development. Recently, China has been in the prior position in discovering of structurally diverse active natural products from natural medicines. In 2018, a series of natural products with novel structures and significant biological activities have been isolated and studied by scholars from China, and 73 molecules with novel carbon frameworks have been selected as "Hot of The Press" by Nat Prod Rep Journal. In this review, the original, structures and biological activities of 123 compounds of natural products research field in 2018 were briefly described, which was aimed to exhibit the highlights of natural products research from China in past year.
Utilization of traditional Chinese medicine (TCM) resources for pharmaceutical development is an important part of modernization of TCM. The classical TCM prescriptions provide an important insight for developing new drugs. Based on the advantages of local TCM resources, focusing on the key scientific problems in the quality evaluation of medicinal materials and the study of classical prescriptions, this research group takes the quality evaluation of medicinal materials as the starting point. Metabolomics serves as a technical means of "quality evaluation of TCM, to support scientific connotation of classical prescriptions and development of new drugs from TCM. Using Radix Bupleurum as an example, this paper systematically and thoroughly expounds the above research ideas and strategies from the aspects:quality evaluation of medicinal materials, basic research of Xiaoyansan, and research and development of new anti-depressants. This provides the scientific basis for the modernization of TCM.
Diabetic kidney disease (DKD) is one of the most serious microvascular complications in diabetic patients, and is the leading cause of end-stage renal disease. The interaction between metabolic and hemodynamic factors leads to activation of the common pathways of diabetic kidney injury. Studies have shown that salvianolic acid can alleviate renal fibrosis and renal injury caused by diabetes by regulating renal tubular interstitial activator A, transforming growth factor-β1 and monocyte chemokine protein-1. It can also participate in the reconstruction of the glomerular extracellular matrix by affecting the expression of protein kinase ERK1/2 protein, which serves a protective effect on diabetic kidneys. Tanshinone can inhibit oxidative stress mediated glucose-induced kidney injury, inhibit the expression of protein tyrosine phosphatase 1B (PTP1B) activity, and improve the secretion function of beta cells in type 2 diabetes mellitus. Interstitial fibrosis in diabetic nephropathy can be alleviated by blocking TGF-β/Smad, NF-κB and Wnt/β-catenin signaling pathway. It has been suggested that salvianolic acid and salvianone are excellent candidates for prevention and treatment of diabetic nephropathy. We provide here the scientific basis for in-depth research and development of salvianolic acid and salvianone into drugs.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) infection remains a major public health problem of global concern, largely due to antibiotics resistance, persistence and immune evasion. Sphingolipid bioactive molecules are involved in several important pathophysiological processes. Sphingosine-1-phosphate is a key product of sphingolipid metabolism, and can play a role in two manners:autocrine and/or paracrine. Sphingosine-1-phosphate regulates T cells and a variety of antigen-presenting cells during M. tuberculosis infection, promotes antigen processing and expression in monocytes, is involved in the maturation of phagolysosome, regulates Ca2+ homeostasis, participates in the autophagy of macrophages, inhibits the survival and proliferation of M. tuberculosis within host cells, and effectively reduces the necrosis of the mouse lungs infected by M. tuberculosis. Injection of 20 nmol per mouse sphingosine-1-phosphate inhibited up to 47% of mycobacterial growth in the lung and spleen of mice infected by M. tuberculosis. In this paper, sphingosine-1-phosphate, its receptors and regulatory network were reviewed, and the specific mechanism of sphingosine-1-phosphate inhibiting the survival of M. tuberculosis-infected host cells was elaborated. This will provide novel insights into the new targets for tuberculosis prevention and treatment.
This research is aimed to investigate the effect of ampelopsin on apoptosis and migration of human hepatoma SMMC-7721 cells and explore the molecular mechanism. SMMC-7721 cells were pretreated with different doses of ampelopsin and cells proliferation was detected by CCK8 kit. Cell morphology was observed under an inverted microscope. Nuclear morphology was detected by DAPI staining. Apoptotic rate was detected by Annexin V-FITC/PI flow cytometry. Migration and invasion were detected by Transwell and scratch healing test. Western blotting was used to detect cleavage of poly ADP-ribose polymerase (PARP), expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-cadherin, and N-cadherin, and phosphorylation of ERK, P38 and JNK in MAPKs pathway. Our results showed that ampelopsin significantly inhibited proliferation and induced apoptosis of SMMC-7721 cells, with half inhibition dose (IC50) for 24 h was 38.98 μg·mL-1. With 50 μg·mL-1 ampelopsin treatment, typical apoptotic morphological changes occurred, such as cell detachment, shrinkage and nuclear condensation. Apoptotic rate increased from 15% to 55.1%, with PARP cleavage significantly increased. In addition, treatment of ampelopsin reduced scratch healing of cells and transmembrane cells number. The expression levels of MMP-2 and MMP-9 were decreased. Further analysis of EMT-related proteins showed that after ampelopsin treatment, E-cadherin was up-regulated and N-cadherin was down-regulated. During ampelopsin treatment, ERK reached its peak of activation after 1 h, while the maximum activation time of JNK was 12 h. Meanwhile, P38 was activated within 4 h, with the highest point at 2 h. But after 4 h, ampelopsin inhibited phosphorylation of P38. These results indicated that ampelopsin induced apoptosis and reduced migration through activating MAPKs pathway and reversing EMT process in SMMC-7721 cells. This work provides a mechanistic basis for utilizing ampelopsin for anti-hepatocarcinoma treatment.
This study aims to develop multifunctional drug delivery system based on hollow mesoporous copper sulfide (HMCuS) nanoparticles. This type of nanoparticles is expected to achieve the synergistic treatment of tumor by targeted phototherapy and chemotherapy. The carrier was synthesized by a substitution method, and the anti-cancer drug doxorubicin (DOX) was loaded and then modified by hyaluronic acid (HA) to prepare the anticancer drug system DOX/HMCuS-HA. The results suggested that DOX/HMCuS-HA presented uniform spherical structure, with the drug loading efficiency of 33.6%, the particle size and zeta potential being 113.8±6.9 nm and 18.4±2.8 mV, respectively. When 100 μg·mL-1 HMCuS was irradiated under 808 nm laser (2 W·cm-2) for 8 min, the temperature can heat up 51℃, demonstrating high photothermal conversion efficacy. Electron spin resonance (ESR) tests and methylene blue degradation experiments showed that HMCuS nanoparticles could simultaneously produce hydroxyl radical (·OH) mediated photodynamic therapy. In addition, HA was responsible for minimizing premature drug release and increasing tumor targeting efficiency by acting as a smart gatekeeper with tumor specific targeting moiety. In vitro drug release experiments showed that the coated HA could be degraded by intracellular lysosomal enzyme hyaluronidase, which facilitated DOX release. The acidic microenvironment of tumor cell and external near infrared (NIR) stimulus could trigger further release of DOX from the nanoparticles. These results point to a new strategy for timely and effective anti-tumor treatment.
Aging is a normal physiological process involving coaction of many factors. The anti-aging effects of natural products have been studied by many domestic and international scholars, but not far enough, which still needed to be explored. Flavonoids, as natural products, have a variety of pharmacological activities and present in many traditional Chinese medicines. In recent years, research results indicate that flavonoids can delay the aging process of the nervous, immune, and reproductive systems, and the liver, skin and other tissues. The anti-aging effects of flavonoids have attracted more and more attention. Therefore, development of anti-aging drugs from flavonoids is of great significance to improve the quality of life for the elderly and slow the process of aging. However, the mechanism of the anti-aging effect of flavonoids remains unknown at present. This review will discuss the anti-aging effect and mechanisms of flavonoids in traditional Chinese medicine from the aspects of cellular signaling pathways and metabolic pathways based on the modern theories of aging.
6-Bromo-3-n-butylphthalide was obtained by nitration, reduction and diazotization from carboxybenzaldehyde. Twenty hybrids from substituted styrene and 6-bromo-3-n-butylphthalide were synthesized and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The mechanism of neuroprotection was investigated by Western blot analyses. The results indicated that most of these compounds had a potent neuroprotective activity (All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine), especially 10h and 10i showed significant effects, which may play a neuroprotective role by activating the PI3K/Akt signaling pathway.
This study aims to investigate the effect of down-regulation of miR-205-5p by transfection of miR-205-5p inhibitor on the sensitivity of HNE1/DDP cells to cisplatin (DDP) induced apoptosis and explore the underlying mechanism. qRT-PCR was used to detect the expression of miR-205-5p in HNE1 or HNE1/DDP cells. The expression level of miR-205-5p was analyzed after transfecting HNE1/DDP cells with miR-205-5p inhibitor. MTT assay was used to evaluate the inhibitory effect of DDP alone or in combination with miR-205-5p inhibitor on the proliferation of HNE1/DDP or HNE1 cells. Apoptosis of cells treated with miR-205-5p inhibitor alone or in combination with DDP (8 μmol·L-1) was assessed using flow cytometry with PI staining, with the nucleus was counterstained with DAPI staining. The expression of Bax, Bak, Mcl-1, or Bcl-2 was analyzed by Western blot. HNE1/DDP cells showed a high level of expression of miR-205-5p, and the expression of miR-205-5p was significantly decreased by transfection of miR-205-5p inhibitor. Down-regulation of miR-205-5p significantly increased the sensitivity of HNE1/DDP cells to DDP (P < 0.05). Transfection of miR-205-5p inhibitor enhanced the sensitivity of HNE1/DDP cells to DDP induced apoptosis. Treatment of HNE1/DDP cells with miR-205-5p inhibitor combined with DDP (8 μmol·L-1) for 24 h resulted in an apoptotic rate of 28.93% ±2.50%, significantly higher than that treated with miR-205-5p inhibitor (9.83% ±1.31%) or DDP alone (10.83% ±1.70%) (P < 0.05). DAPI staining showed that HNE1/DDP cell nucleus became significantly condensed and fragmented in miR-205-5p inhibitor combined with DDP group. The combined group up-regulated the expression of Bax and down-regulated the expression of Bcl-2 in HNE1/DDP cells. Therefore, down-regulation of miR-205-5p can enhance the sensitivity of HNE1/DDP cells to cisplatin induced apoptosis, and the mechanism may involve up-regulation of Bax and down-regulation of Bcl-2 expression.
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