Experimental study of cardioprotective effects of Cinnamomi Ramulus and Cinnamomi Cortex formula granules on myocardial ischemia/reperfusion injury in rats based on efficacy of "warming and coordinating heart Yang" / 中国中药杂志

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1β(IL-1β), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1β, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1β in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.

Relationship between pyroptosis and cardiovascular diseases and traditional Chinese medicine prevention and treatment research / 中国中药杂志

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.

Improving Effect of L-leucine on Memory Impairment in Plateau / 医药导报

Objective To explore the improving effect of L-leucine on memory impairment in plateau and the mecha-nism. Methods After successfully trained in the 8-arm radial maze,50 male Kunming mice were selected and randomly divid-ed into normoxic control group (NC group),model group,and L-leucine (low,medium and high dose) groups.Animals in L-leu-cine groups were intragastrically given 0.473 g?kg-1 ,0.945 g?kg-1 and 1.89 g?kg-1 L-leucine for 7 days and those in NC and model control groups were administered the same volume of purified water for the same period of time.At the 4th day of the treat-ment,the mice in the model control group and L-leucine groups were placed in a large low-pressure and low-oxygen chamber to simulate low-pressure hypoxic environment of the plateau (7 500 m,3 d).The 8-arm radial maze was used to measure the spatial learning and memory ability of mice and dry-wet method to measure the water content of brain tissue.HE staining was employed to observe the cell morphological changes in CA1 region of the hippocampus.The expression levels of mTOR,P70S6K and 4E-BP1 mRNA in the hippocampus were detected by SYBR Green real-time PCR. Results The reference memory error ( RME) ,total error ( TE) ,testing time ( TT) ,and water content of brain tissue were significantly increased,the neuron injury was exacerbated in CA1 region of the hippocampus,and the expression levels of mTOR and P70S6K mRNA were markedly decreased in model control group when compared with those in NC group (P<0.05 or P<0.01).These indexes,however,were significantly improved in L-leu-cine groups,especially in high-dose group. Conclusion L-leucine can improve memory impairment in plateau,and the mecha-nism may involve the activation of mTOR and its downstream substrates (4E-BP1 and P70S6K).

Protective effect of phenylethanoid glycosides extracted from phlomis younghusbandii on acute high altitude pulmonary edema in rats / 解放军医学杂志

Objective To investigate the protective effect of phenylethanoid glycosides (PhGCs) extracted from Phlomis younghusbandii on acute high altitude pulmonary edema (HAPE) in rats. MethodsSeventy male Wistar rats were randomly divided into 7 groups (10 each): normoxia control group (NG, distilled water), normoxia+PhGCs group (NG+PhGCs, 400mg/ kg), hypoxia model group (HG, distilled water), dexamethasone (Dex, 4mg/kg), and three groups of PhGCs in high (PhGCs-H, 400mg/kg), middle (PhGCs-M, 200mg/kg) and low (PhGCs-L, 50mg/kg) dosage. PhGCs extracted from Phlomis younghusbandii were administered prophylactically to rats for 3 days, and HAPE was induced by the hypobaric hypoxia exposure for 72 hours in an animal decompression chamber with the chamber pressure of 267mmHg to simulate an altitude of 8000m. The water content of rat lung tissue was determined with wet/dry specific gravity method, and histopathologic changes were observed with HE staining. The enzymatic activities of SOD and GSH, and the contents of MDA in lung tissue were determined with spectrophotometry, and the contents of IL-1β, TNF-α in serum and lung tissue were determined with ELISA. ResultsCompared with NG group, no obvious difference was found in the water content of rat lung tissue in NG+PhGCs group, but the water content increased obviously in HG group (P<0.05). Compared with NG group, lung tissue congestion and edema were found in HG group, with a heavy inflammatory cell infiltration, widening of alveolar interval, and thickening of alveolar wall were found. The enzymatic activities of SOD and GSH were notablely depressed, and the contents of MDA in lung tissue, and the contents of IL-1β and TNF-α in serum and lung tissue remarkably increased (P<0.05). Compared with HG group, the water content of rat lung tissue in each PhGCs group decreased obviously. Inflammatory cells infiltration, widening of alveolar interval, and thickening of alveolar wall, the enzymatic activity of SOD and GSH increased, and the contents of IL-1β, TNF-α and MDA decreased significantly in PhGCs groups (P<0.05). Conclusion PhGCs extracted from Phlomis younghusbandii may alleviate the oxidative stress and inflammatory response of acute lung injury induced by acute hypoxia. PhGC showed a protective effect against acute HAPE in a rat model.

Improving Effect of Phenylethanoid Glycosides from Tibetan Medicine Phlomis younghusbandii on Rats with Acute High-altitude Cerebral Edema / 中国药房

OBJECTIVE:To investigate the improving effect of phenylethanoid glycosides (PhGCs) from Tibetan medicine Phlomis younghusbandii on rats with acute high-altitude cerebral edema. METHODS:60 Wistar rats were randomly divided into a normoxia control group (isometric sterile water for injection),a hypoxia model group (isometric sterile water for injection),a dexamethasone group(4 mg/kg),and three groups of PhGCs at high(400 mg/kg),middle(200 mg/kg)and low(50 mg/kg)dos-es,with 10 rats in each group. The rats were given drugs,ig,6 d before the establishment of models. On the 4th day of administra-tion,ig,the rats in all groups except the normoxia blank group were placed in a simulated 8 000 m altitude plateau environment for 72 h hypoxic exposure to establish the rat models of high-altitude cerebral edema. Following HE stain,the pathological changes in rats’brain tissues were observed under the light microscope. Dry-wet proportion method was used to determine the water con-tents in rats’brain. The content of MDA and the activities of SOD and GSH in rats’brain tissues were detected. Enzyme-linked im-munosorbent assay was adopted to determine the contents of IL-1β and TNF-α in rats’serum and brain tissues. RESULTS:Com-pared to the rats in the normoxia control group,those in the hypoxia model group showed obvious brain edema,and thickened lacu-nas around cells and vessels and inflammatory cell infiltration, higher water contents and MDA and weaker activities of SOD and GSH in brain,and higher contents of IL-1β and TNF-α in serum and brain tissues. There were statistically significances (P<0.01 or P<0.05). Compared to the rats in the hypoxia model group,those in the groups of PhGCs at high,middleand low dosages demonstrated less inflammatory cell infiltration and lower water contents in brain tissues,in which the groups of PhGCs at high and middle dosages demonstrated lower content of MDA and stronger activities of SOD and GSH in brain tissues, and lower contents of IL-1β and TNF-α in serum and brain tissues. There were statistically significances (P<0.01 or P<0.05). CONCLUSIONS:PhGCs can obviously alleviate the acute cerebral injury in rats which is caused by acute hypoxia and has im-provement effect to some degree on the rats with acute high-altitude cerebral edema.