Paeonol is a major phenolic micromolecular component of Moutan cortex Radicis, a traditional Chinese Medicine. It has shown antitumor effects in previous studies; however, the underlying mechanisms remain unknown. This study investigated the mechanism by giving treatments of placebo, cyclophosphamide, paeonol of 150 and 300 mg/kg to 4 groups of mice bearing EMT6 breast cancer. Apoptosis in tumor cells were confirmed by morphology analysis, including hematoxylin, eosin staining and TUNEL staining. The results showed that the weight of EMT6 breast tumor was significantly reduced in the groups treated with both 150 and 300 mg/kg of paeonol. Immunohistochemical and Western blot results showed that the expression of Bcl-2 was down-regulated while the expression of Bax, caspase 8 and caspase 3 was up-regulated respectively. These results suggest that paeonol exhibits antitumor effects and the mechanism of the inhibition is via induction of apoptosis, regulation of Bcl-2 and Bax expression, and activation of caspase 8 and caspase 3.
Animals ; Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Caspase 3 ; Caspase 8 ; Cyclophosphamide ; Eosine Yellowish-(YS) ; Hematoxylin ; In Situ Nick-End Labeling ; Medicine, Chinese Traditional ; Mice* ; Phenol

PURPOSE: Diabetes is the leading cause of end-stage renal failure. The present study was undertaken to characterize the effects of Corni Fructus on diabetic nephropathy in streptozotocin-induced diabetic rats and their mechanisms. MATERIALS AND METHODS: Streptozotocin-diabetic rats were orally administrated with Corni Fructus at a dose of 100, 200 or 400 mg/kg body mass for 40 days. RESULTS: Corni Fructus-treated diabetic rats showed significant decreases of blood glucose, urinary protein levels and water consumption. Corni Fructus also reduced serum total cholesterol, total triglyceride and low-density lipoprotein cholesterol levels, and showed a tendency of enhancing high-density lipoprotein cholesterol level. Levels of serum albumin and creatinine in diabetic rats were also significantly reduced by Corni Fructus administration at a dose of 200 and 400 mg/kg body mass compared with non-treated diabetic rats. Corni Fructus increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidose (GSH-px) activities in the kidneys of diabetic rats. Furthermore, Corni Fructus treatment enhanced renal peroxisome proliferator-activated receptor-gamma (PPARgamma) expression in diabetic rats. CONCLUSION: These results demonstrated that Corni Fructus may have the potential to protect the animals from diabetic nephropathy by amelioration of oxidative stress and stimulation of PPARgamma expression.
Animals ; Blotting, Western ; Body Weight/drug effects ; Catalase/metabolism ; Cornus/*chemistry ; Diabetes Mellitus, Experimental/*drug therapy ; Glucose Tolerance Test ; Glutathione/metabolism ; Hypoglycemic Agents/*therapeutic use ; Male ; Malondialdehyde/metabolism ; Plant Extracts/*therapeutic use ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase/metabolism

Objective:To analyze the medication rule of treating orthopedics in Tibetan Medicine by data mining, in order to summarize the characteristics and theory of ethnic minorities medicine for treating orthopedics and traumatology.Methods:By collecting the treatment methods of orthopedics and traumatologic diseases in books of Chinese Materia Medica·Tibetan Medicine Volume and Chinese Medical Encyclopedia·Tibetan Medicine to analyze the frequency, cluster and association rules of Tibetan Medicines by using Office Excel 2019, IBM SPSS Statistics 26.0 and IBM SPSS modeler 14.1 respectively. Results:Among the 202 Tibetan Medicine prescriptions of Orthopedic Department, 338 belongs to Chinese medicines. The top 3 Chinese medicines that are frequently appeared are Chebulae Fructus, Inula racemosa Hook.f, and Carthami Flos. The properties of those medicines are mainly cold, warm and cool, and the tastes are mainly pungent, bitter and sweet; the meridians mainly belong to liver, lung, stomach and spleen; The priscriptions mainly cover four kinds of diseases: trauma, arthralgia syndrome, lumbosacral tendon injury, chest and back tendon injury. The four kinds of cluster combinations were obtained. The core Chinese medicines were Chebulae Fructus, Terminaliae Belliricae Fructus, Phyllanthi Fructus, Cassiae Semen, Olibanum, Abelmoschus moschatus, and the common medicine pair were Chebulae Fructus- Terminaliae Belliricae Fructus, Abelmoschus moschatus- Cassiae Semen, Olibanum- Abelmoschus moschatus and so on. Conclusions:Tibetan Medicines treat orthopedics and traumatological diseases with antipyretic medicines as the main yellow water, followed by blood activating, Qi regulating and wind dampness removing medicines. With Sanguo Decoction and Sanhuang water of Tibetan medicine as the core, they are often combined with other antipyretic and blood cooling medicines and bone connecting medicines. Tibetan Medicine pays attention to the application of dry yellow water theory, which reflects the role of the core theory of Qingxie method and yellow water theory of Tibetan Medicine in the diagnosis and treatment of orthopedic and traumatologic diseases.

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.