Shaofu Zhuyu Decoction attenuates fibrosis in endometriosis through regulating PTEN/Akt/mTOR signaling pathway / 中国中药杂志

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.

Effect of Modified Shaofu Zhuyutang on Neural Angiogenesis and Pelvic Pain of Endometriosis with Syndrome of Cold Congeal and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical curative effect of modified Shaofu Zhuyutang on pelvic pain of endometriosis （EMT） with syndrome of cold congeal and blood stasis and the influence on neural angiogenesis. MethodA total of 110 cases were divided into a control group （54 cases） and an observation group （56 cases） by the random number table method. Patients in the control group took Aifu Nuangong pills with 6 g/time and 2 times/day. Patients in the observation group took modified Shaofu Zhuyutang with 1 dose/day. Course of treatment continued for 3 menstrual cycles. Dysmenorrhea， other symptoms and signs of pelvic pain， and the EMT health profile-5 （EHP-5） for patients with syndrome of cold congeal and blood stasis and EMT were scored before and after treatment. The levels of peripheral blood nerve growth factor （NGF）， substance P （SP）， calcitonin gene-related peptide （CGRP）， brain-derived neurotrophic factor （BDNF）， soluble Fms-like tyrosine kinase（sFlt-1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9）， and insulin growth factor-1 （IGF-1） were detected before and after treatment. The levels of prostaglandin E2 （PGE2）， cyclooxygenase-2 （COX-2）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and other inflammatory factors were detected before and after treatment. The pain medication usage and recurrence were recorded. ResultThe scores of dysmenorrhea， symptoms of pelvic pain symptoms （non-menstrual pelvic pain， dyspareunia， anal falling pain， and defecation pain， etc.）， and signs of pelvic pain （pelvic tenderness and sacral ligament tender nodules） in the observation group were lower than those in the control group （P<0.01）. The disappearance rates of dysmenorrhea， pelvic tenderness， and sacral ligament tender nodules were 67.35% （33/49）， 73.33% （33/45）， and 77.27% （34/44） in the observation group， which were all higher than 45.83% （22/48）， 48.84% （21/43）， and 52.27% （23/44） in the control group. The difference was statistically significant （χ2=4.571， χ2=5.565， χ2=6.026， P<0.05）. The scores of EHP-5 and syndrome of cold congeal and blood stasis in the observation group were lower than those in the control group （P<0.01）. The levels of VEGF， MMP-9， IGF-1， NGF， SP， CGRP， and BDNF in the observation group were lower than those in the control group （P<0.01）， while the level of sFlt-1 was higher than that in the control group （P<0.01）. The levels of PGE2， COX-2， TNF-α， and IL-6 in the observation group were lower than those in the control group （P<0.01）. The total effective rate of the observation group was 92.45% （49/53）， which was higher than 76.00% （38/50） of the control group （χ2=5.307， P<0.05）. After 6 months of follow-up， the recurrence rate in the observation group was 30.61% （15/49）， which was lower than 52.63% （20/38） in the control group （χ2=4.315， P<0.05）. The average of taking ibuprofen sustained-release capsules in the control group was higher than that in the observation group per menstrual period （P<0.01）. ConclusionModified Shaofu Zhuyutang treated pelvic pain of EMT with syndrome of cold congeal and blood stasis by regulating the mechanism of neural angiogenesis， reducing pain， and promoting the disappearance of related pains， thus improving the quality of life. Shaofu Zhuyutang has a better clinical effect than Aifu Nuangong pills and has a low recurrence rate.

Effects of Radix Hedysari, Radix Astragalus and compatibility of Angelica Sinensis on blood deficiency model mice induced by cyclophosphamide / 中国应用生理学杂志

OBJECTIVE@#To study the intervention effects of Radix Hedysari, Radix Astragalus and compatibility of Angelica Sinensis on blood deficiency model mice induced by cyclophosphamide (CTX).@*METHODS@#The mice were randomly divided into 7 groups, 10 mice each group. The blood deficiency model was established by CTX. The blank group and model group were treated with saline by gavage, while mice in positive group were administered with Lvjiaobuxue granule. Four dosage group were administered with Radix Hedysari, Radix Hedysari-Radix Angelica Sinensis(5:1), Radix Astragalus and Radix Astragalus-Radix Angelica Sinensis(5:1) water decoction. All the drugs were administered to mice for consecutive 7 d. The contents of red blood cell (RBC), lymphocyte(LYM), hematocrit (HCT), white blood cell (WBC), platelet (PLT) were detected by hematology analyzer, while thymus index(TI), spleen index(SI), reticulocyte (RC), marrow karyocyte (MK) were calculated, and the femur by pathological section were observed by microscope.@*RESULTS@#Compared with blank group, the contents of RBC, WBC, HCT, PLT, LYM were decreased in model group (<0.05). Compared with model group, the contents of RBC, WBC, HCT, PLT, LYM, RC and marrow karyocyte were increased in Hedysari-Angelica Sinensis(5:1) and Astragalus Angelica Sinensis(5:1) (<0.05), at the same time, the pathological damage of femur could be improved.@*CONCLUSIONS@#The effect of enrichment blood on blood deficiency model mice in Hedysari-Angelica Sinensis (5:1) and Astragalus-Angelica Sinensis(5:1) were superior to Hedysari and Astragalus.

Molecular mechanism of Shaofu Zhuyu decoction in treating endometriosis dysmenorrhea based on GPER2/MAPK/STAT1 axis / 中国中药杂志

The aim of this paper is to study the molecular mechanism of Shaofu Zhuyu decoction in treating dysmenorrhea of endometriosis based on GPER2/MAPK/STAT1 axis. In this study, HE staining was used to observe the pathological changes of the rats in each group. The levels of TNF-α and IL-6 were detected by ELISA assay. The mRNA expressions of neurotransmitter receptor (NK1) and GPER were detected by qPCR. The protein contents of MAPK and STAT1 were detected by Western blot. According to the results, compared with the model group, Shaofu Zhuyu decoction could significantly improve the inflammation of the ectopic uterine cavity tissue, decrease the contents of TNF-α and IL-6 in the uterine cavity, the mRNA expressions of NK1 and GPER, and the protein expressions of MAPK and STAT1. In conclusion, Shaofu Zhuyu decoction could effectively inhibit the expressions of GPER2, MAPK and STAT1, decrease the levels of TNF-α, IL-6 and NK1 mRNA and relieve the inflammatory pain in patients with endometriosis.