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

ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND METHODS: The chemical components of ECP were determined by high-performance liquid chromatography and gas chromatography-mass spectrometry. SD rats were randomly divided into Sham, MCAO, Nim (20.00 mg/kg), and ECP (1.33 and 2.00 g/kg) groups, with 13 animals in each group. After 14 days of oral administration, we established a model of cerebral ischemia reperfusion injury by blocking the middle cerebral artery of rats. After 24 h of reperfusion injury, we evaluated the protective effect of ECP on ischemic brain by neural function score, TTC, H&E and Nissl staining. TUNEL fluorescence, western blot and immunohistochemistry were used to detect the phenomenon of apoptosis and the expression of apoptosis-related proteins Bax, Bcl-2, Cyto-c and activated Caspase-3. Furthermore, western blot, qRT-PCR and immunohistochemistry were employed to detect CaMKⅡ, ATF4 and c-Jun gene and protein expression. RESULTS: ECP contains agarotetrol, eugenol, oleanolic acid, ursolic acid, dehydrodiisoeugenol, hydroxysafflor yellow A, kaempferide, gallic acid, alantolactone, isoalantolactone, costunolide, dehydrocostus lactone, brucine, strychnine, echinacoside, bilirubin and cholic acid. Compared with MCAO group, ECP can significantly ameliorate the neurological deficit of cerebral ischemia in rats and reduce the volume of cerebral infarction. Pathological and Nissl staining results showed that ECP sharply inhibited the inflammatory infiltration injury of neurons and increased the activity of neurons in comparation with the MCAO group. TUNEL fluorescence apoptosis results confirmed that ECP obviously inhibited the apoptosis of neurons. Meanwhile, the results of immunohistochemistry and western blot demonstrated that EPC can dramatically inhibit the expression of pro-apoptotic proteins Bax, Cyto-c and activated Caspase-3, while increase the level of anti-apoptotic protein Bcl-2. In addition, compared with MCAO group, CaMK Ⅱ gene and protein expression were improved significantly by ECP administration. while, the expression of ATF4 and c-Jun genes and proteins were decreased. CONCLUSIONS: In conclusion, this study preliminarily demonstrated that the protective effect of ECP on ischemic brain is related to the improvement of neurological deficit, reducing the size of cerebral infarction, improving the activity of neurons, inhibiting the mitochondrial apoptosis pathway by regulating the protein expression of CaMKⅡ, ATF4 and c-Jun. However, further in vivo and in vitro investigations are still needed to clarify the underlying mechanism of ECP in treating cerebral ischemia sequelae.

[Study on regularity of Tibetan medicine in treatment of gZav-Grib disease (apoplexy sequelae) based on HIS clinical medical records].

This research is launched to look for the medication rules and characteristics of Tibetan medicine in the treatment of gZav-Grib( apoplexy sequelae). HIS records of gZav-Grib patients were selected from the Tibetan Hospital of Tibet Autonomous Region and Tibetan Hospital of the city of Naqu. SPSS Modeler,Gephi and other data mining and visualization software were used to study the actual law of drug use in the treatment of gZav-Grib in Tibetan medicine. Finally,479 cases of gZav-Grib patients in Tibetan medicine were included. Their average age is 63 and average hospital stay was 32 days. In total,82 Tibetan medicine prescriptions were used for treating gZav-Grib. The frequency in the front is Twenty-flavor Chenxiang Pills( 338 times),Ruyi Zhenbao Pills( 322 times),and Seventy-flavor Zhenzhu Pills( 315 times). According to the regularity of Tebitan medicine,they were applied in different time periods including the early morning,morning,noon,and evening,for example,in the early morning: Seventy-flavor Zhenzhu Pills,morning: Ruyi Zhenbao Pills,noon: Eighteen-flavor Dujuan Pills,evening: Twenty-flavor Chenxiang Pills. In the clinical joint,18 groups were found in the 10% support and 70% confidence. There are two prescriptions confidence more than 80% which nature focus on Gan,Ruan,Xi,Liang,Dun,Han,Wen. gZav-Grib of Tibetan medicine can be divided into two types: r Lung-Grib type and k Hrag-Grib type,in which the medicine of r Lung-Grib type takes Seventy-flavor Zhenzhu Pills as the core prescription,while the medicine of k Hrag-Grib type takes Ruyi Zhenbao Pills as the core prescription. It is found that the treatment of gZav-Grib by Tibetan medicine is mainly dominated by the treatment idea about " Therapeutic r Lung and blood,Consideration of venous diseases". Treatment functions is promoting the circulation of Qi,clearing blood heat and getting rid of bad blood,achieving the purpose of treating both principal secondary aspect of gZav-Grib. The research methods based on the HIS can't only optimize the Tibetan treating gZav-Grib sequela treatment plan and rule of medication,but also provide the scientific basis for Tibetan medicine treat gZav-Grib.

[Study on regularity of drug use in Tibetan medicine treating hypertension based on multi-center clinical medical records and "prescription-property-efficacy-disease"].

This study aimed to explore the rule of Tibetan medicine in clinical treatment of hypertension( k Hrag-rLung-stod-vtshangs) and analyze the characteristics of its prescriptions. One hundred and thirty-seven cases of hypertension treated Tibetan medicine were collected. Data mining,Gephi,Cytoscape and other methods and software were used to analyze the characteristics of Tibetan medicine. The results showed that there were 44 cases of r Lung-type hypertension in clinical medical records,while 57 cases of k Hrag-type hypertension. There were 103 treatment prescriptions. The frequency of these prescriptions covered Twenty-five Yuganzi Pills( 96 times),Seventy Pearl Pills( 80 times),Eight Chenxiang Pills( 75 times),and Sanwei Ganlu Powder( 62 times),and they were highly correlated,with confidence greater than 95%. There were 332 prescriptions involved in the prescriptions which is core prescription medicines. This study first proposed the dosage analysis method of Tibetan medicine prescription medicines,and obtained the more dosage of Chebulae Fructus,Phyllanthi Fructus,Aucklandiae Radix,Aquilariae Lignum Resinatum and so on. The correlation analysis of the prescription medicines found that Carthami Flos,Myristicae Semen,Bambusae Concretio Silicea,Caryophylli Flos,Amomi Fructus Rotundus led by Tsaoko Fructus had a high correlation and a confidence greater than 75%. These herbs were guaranteed when Tibetan medicine was used in combination. The key drugs for protecting viscera and regulating the three gastric fires. The prescription is mainly cold,blunt,sparse and rough. Its efficacy focuses on the pathogenesis of blood fever,blood stickiness and venous blockage caused by heat,sharpness,odor and stickiness. It mainly treats Tibetan medicine diseases such as k Hrag-r Lung-stod-vtshangs and k Hrag-vpel( polyemia). It is suggested that Tibetan medicine has a three-in-one invisible treatment principle of " clearing blood-heat,opening vessel and regulating stomach-fire" in the treatment of hypertension,which attributed to both cardiovascular function and gastrointestinal metabolic function. This may be a significant and invisible knowledge of Tibetan medicine in the treatment of hypertension.