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Objective: To analyze the pharmacological basis and molecular mechanism of Sanjie Zhentong capsule in the treatment of endometriosis, adenomyosis, secondary dysmenorrhea. Method: The 6 compounds of Sanjie Zhentong capsule showed stronger interactions with 87 proteins relating to endometriosis, adenomyosis, and secondary dysmenorrhea in molecular docking. Then the drug-target network was selected, and the network features were analyzed. Result: The molecular docking and network characteristics revealed 5 main active molecules and 23 potential targets of Sanjie Zhentong capsule. Conclusion: The main active ingredients of Sanjie Zhentong capsule have a trong inhibition effect on endometrial angiogenesis and blood circulation, uterine smooth muscle contraction, immune inflammatory reaction and estrogen secretion by acting on the targets of inflammation, cell invasion, metastasis, coagulation system, smooth muscle contraction and neurohormone regulation, so as to treat endometriosis, adenomyosis and secondary dysmenorrhea.
ABSTRACT
Objective: The anti-inflammatory and anti-fibrotic effects of Sanjie Zhentong Capsule (SJZT) on chronic pelvic inflammation in rats were investigated and its underlying mechanisms were explored. Methods: Ten rats regarded as normal group with sham operation were randomly selected from 60 female SD rats, and the remaining rats were injected with phenol mucilage in the left uteri to replicate chronic pelvic inflammatory disease. On day 14, after the operation, according to body weight, the 50 rats were randomly allocated to model group, dexamethasone (DEX) group, SJZT low dose group (0.192 g/kg), SJZT middle dose group (0.384 g/kg), and SJZT high dose group (0.768 g/kg). The drugs were dissolved in 0.5% CMC-Na solution and administered respectively, while 0.5% CMC-Na solution was given to the normal and model group. After all the animals were treated by oral gavage once a day for 30 d, the blood and the left uteri were collected. The uterine tissues were fixed and stained with haematoxylin-eosin (HE) and Masson’s trichrome for histopathology examination and the concentrations of TNF-α, IL-1β, PDGF, and TIMP in serum were assayed by ELISA. The protein expression levels of p-ERK1/2, p-JNK, NF-κB p65, MMP-2, and MMP-9 in the uteri were also detected by Western blotting. Results: Compared with the model group, SJZT could effectively improve the arrangement disorder of cavity wall, reduce the degeneration and necrosis of epithelial cells, the infiltration of inflammatory cells and the congestion of lamina propria, and alleviate the proliferation of collagen fibers in lamina propria. SJZT could also reduce the concentrations of TNF-α, IL-1β, PDGF, and TIMP in serum. Moreover, the protein expression of p-ERK1/2, p-JNK, and NF-κB p65 in the uteri were inhibited significantly, and at the same time the protein expression of MMP-2 and MMP-9 was increased markedly by SJZT. Conclusion: SJZT exhibits robust anti- inflammatory and anti-fibrosis effects in chronic pelvic inflammatory disease model induced by phenol mucilage. Its mechanisms may be related to regulating NF-κB and MAPK signaling pathways, inhibiting inflammation, reducing the synthesis of extracellular matrix (ECM), increasing the degradation of ECM and promoting the repair of fibrosis.
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AIM@#To analyze the composition of the Chinese herbal medicine Sanjie Zhentong Capsule (SJZTC) and test the therapeutic efficacy of each component in a rat model of endometriosis.@*METHODS@#A rapid resolution liquid chromatography (RRLC) method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS) has been developed for the analysis of SJZTC. Two main ingredients, Drac(h)onis sanguis and saponin, were tested in the endometriosis model. Sixty Lewis female rats were in the estrous cycle stage when endometriosis was experimentally initiated by peritoneal implantation of endometrial tissue. Four weeks later, a second laparotomy was performed and implant volumes were measured. After that, the implanted rats were randomized into five study groups: control group (treatment with saline), anastrozole group (treatment with anastrole, 18 μg per day), loureirin A group (treated with loureirin A, 97.2 mg), ginsenoside Re group (treated with ginsenoside Re, 64.8 mg), and SJZTC groups (treated with SJZTC, 86.4 mg) administered once a day for 4 weeks via gastric gavage. After four weeks of treatment, a third laparotomy was performed, implant volumes were re-measured, and the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were tested.@*RESULTS@#A total of 38 compounds including, both the target and unknown compounds, were rapidly predicted in the capsule extract by the developed method. Compared with the control group, the anastrozole group, loureirin A group, ginsenoside Re group, and SJZTC treated group showed smaller implant volumes, as well as lower levels of VEGF and TNF-α in the peritoneal focus (P < 0.01 for all comparisons). Furthermore, parameters in the groups treated with SJZTC, loureirin A and ginsenoside Re were significantly better than the control group and the anastrozole group. These results indicate that SJZTC and its two main components are effective in reducing the development of endometriosis.
Subject(s)
Animals , Female , Humans , Rats , Capsules , Chemistry , Disease Models, Animal , Drugs, Chinese Herbal , Chemistry , Endometriosis , Drug Therapy , Rats, Inbred LewABSTRACT
This study was aimed to establish a HPLC fingerprint of saponins in Sanjie-zhentong Capsule in order to make a quantitative analysis of the quality of Sanjie-zhentong Capsule. The Waters Symmetry ShieldTM RP18 (4.6 mmí 250 mm, 5 μm) column was used with a mobile phase of acetonitrile-water gradient elution. The flow rate was 1.2 mL/min. The column temperature was 30℃. The detection wavelength was 203 nm. The results showed that the fingerprint chromatography included 9 mutual peaks. The similarity among batches was more than 0.95. Compared with reference substance, five characteristic components were recognized. The five components are notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd. It was concluded that this method was rapid, simple and accurate and can be used as one of the effective methods for the quality control of Sanjie-zhen-tong Capsule.