Betel Shi-San-Wei Ingredients Pill(BSSWIP) was first recorded in the 19th century writings Meng-Yi Jin-Gui with the name of Gao-Y ou-13. The name of BSSWIP was first recorded in the book of the 1977 edition of the Drug Standard of the Jilin Province, which was formerly known as Tai De Hu Ran Gu Lu Ge Qi Nai Ran Ta, Se Me Ji De Ji De, and etc. Although in the book of Tong-Wa-Ga-Ji-De, Se Me Ji De Ji De was documented, it was the same name of different compositions. It had no original relation with BSSWIP. In different periods, the BSSWIP was consisted of 13, 14 or 15 kinds of herbs. There were at least five different types of herbs appeared in the Gao-Y ou-13. The evolution of prescription was mainly from the 19th century to the first half of the 20th century. There was no major change on prescription composition and proportion since 1971. Among them, 10 kinds of herbs, which were Bing-Lang, Guang-Zao, Mu-Xiang, Ding-Xiang, Rou-Dou-Kou, Zi-Nao-Sha, Gan-Jiang, Bi-Ba, Hu-Jiao, and Chen-Xiang were fixed. The ratio of single herbal medicine changed the most was Zhi-Cao-W u, which was followed by Mu-Xiang, Ding-Xiang and Chen-Xiang. There were no marked sources of BSSWIP in the recording of the Drug Standard of the Jilin Province and the Mongolian Medicine V olume·Ministry of Health of the People's Republic of China. The composition and proportion were considered to be from the book Meng-Y i Jin-Gui according to notes of Standards on Mongolian Patent Medicine in Inner Mongolia. Recordings of three standards are in consistence with the Meng-Y i Jin-Gui on Gao-Y ou-13 except for Y e-Mao-Niu Xin and the different ratio of Zhi-Cao-W u. In the appendix of the Standards on Mongolian Patent Medicine in Inner Mongolia, it marked the differences from the original prescription. Therefore, the other two criteria should also mark the similarities and differences compared with the original prescription properly.

The renal toxicity of rats after a single dose ofMeng-Gen-Wu-Su (mercury) processed products,Meng-Gen-Wu-Su (mercury)-18-composition pill, mercuric sulfide, mercuric chloride, and mercurous chloride was studied. Fifty-four male Wistar rats were randomly divided into nine groups according to body weights (6 rats in each group): normal control group, low and high dose groups (0.033, 0.33 g·kg-1·d-1) ofMeng-Gen-Wu-Su (mercury) processed products, low and high dose groups (0.29, 2.9 g·kg-1·d-1) ofMeng-Gen-Wu-Su (mercury)-18-composition pill, simplified prescription ofMeng-Gen-Wu-Su (mercury)-18-composition pill group (0.26 g·kg-1·d-1), mercuric sulfide group (17.39 mg·kg-1·d-1), mercuric chloride group (4.06 mg·kg-1·d-1) and mercurous chloride group (35.3 mg·kg-1·d-1). After acclimation for one week, once oral administration was given to each group of rats. After 24 h, function and morphological changes of liver and kidney were detected. Mercury accumulation in kidney was determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) and inductively coupled plasma source mass spectrometer (ICP-MS). Apoptosis of renal cell was determined by terminal-deoxynucleoitidyl transferase mediated Nick End Labeling (TUNEL). Renal typeⅢ collagen protein's expression was determined by immunohistochemical (HIC) method and expression changes of MT-1, MT-2 mRNA in kidney were also determined by real-time fluorescence quantitative PCR (real-time-PCR). There was no significant difference of ALT, AST in serum between normal control group and other groups (P>0.05). CREA and UREA in mercurous chloride group were apparently higher than normal control group and low dose group of Meng-Gen-Wu-Su processed products (P<0.01). Hepatic and renal pathologic examination results showed that liver cell of low dose groups ofMeng-Gen-Wu-Su processed products andMeng-Gen-Wu-Su-18-composition pill swelled to a low degree and glomerular disease was not obvious. In high-dose groups ofMeng-Gen-Wu-Su processed products,Meng-Gen-Wu-Su-18-composition pill and mercuric sulfide group, liver and kidney appeared some pathological changes and such changes were more significant in mercuric chloride and mercurous chloride groups. Compared with normal control group and low dose group ofMeng-Gen-Wu-Su processed products, the mercury kidney volume in mercuric chloride and mercurous chloride groups increased significantly (P<0.01). The apoptosis rate of renal cell and expression of typeⅢ collagen protein increased significantly in the groups of mercuric sulfide, mercuric chloride and mercurous chloride (P<0.01). MT-1and MT-2 mRNA gene expression rised significantly in the groups of mercuric chloride and mercurous chloride (P<0.05 orP<0.01). In summary, the rats renal toxicity after a single dose ofMeng-Gen-Wu-Su (Mercury) processed products or MongolianMeng-Gen-Wu-Su (Mercury)-18-composition pill were both far less than that of mercuric chloride or mercurous chloride.

Meng-Gen-Wu-Su (mercury)-18-composition pill was firstly recorded in the book of Gan-Lu-Si-Bu with the name of Jin-18 pill . The name of Me ng-G e n-W u-Su ( mercury )-18-composition pill was firstly recorded in the book of Me ng-Y i-Jin-G ui . Its composition and dosage had always been adjusted in the later dynasties . Until the issue of the book Ne i-Me ng G u-Me ng Che ng-Y ao Biao-Zhun , the composition and dosage of Meng-Gen-Wu-Su was promulgated. In different periods, the Meng-Gen-Wu-Su consisted of 17, 18 or 19 kinds of herbs. There are at least five different types of herbs appeared in the Meng-Gen-Wu-Su-18-composition pill. But 16 kinds of medicinals such as mercury, He-Zi, Cao-Wu, Liu-Huang, Qing-Ma-Zi, Jue-Ming-Zi, Bai-Yun-Xiang, Mu-Xiang, Shi-Chang-Pu, Su-Ge-Mu-Le, Shi-Gao, Rou-Dou-Kou, Ding-Xiang, Cao-Guo, Hong-Hua, Hei-Yun-Xiang are fixed in the composition. The proportion of Meng-Gen-Wu-Su-18-composition pill is inconsistent in different periods. The significant difference of drug dosage proportion are Liu-Huang and Bai-Yun-Xiang, followed by Qing-Ma-Zi, Jue-Ming-Zi, Cao-Guo, Wen-Guan-Mu. The Meng-Gen-Wu-Su-18-composition pill and Jin-18 pill from the book of Gan-Lu-Si-Bu are same prescription with the same composition but different names. The composition and dosage proportion of Meng-Gen-Wu-Su-18-composition pill from the book of Meng-Yi-Jin-Gui and He-Li-Le Jing-Zhu Jie-Y i Nan-Jing are the same with the same prescription name .

OBJECTIVETo observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats.

METHODSixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA).

RESULTThe AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill.

CONCLUSIONThe AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Adenylyl Cyclases ; genetics ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; genetics ; metabolism ; Depression ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Hippocampus ; drug effects ; metabolism ; Humans ; Male ; Mice ; Prefrontal Cortex ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects