ABSTRACT
Xiaoyaowan has the effects of soothing the liver， invigorating the spleen， regulating menstruation， and nourishing blood. It is often used to treat the distending pain of the chest and hypochondriac， loss of appetite， dizziness， and irregular menstruation caused by liver depression and spleen deficiency. The formula originated from the Sinisan of Treatise on Cold Damage（《伤寒论》） in the Han dynasty and was officially formulated in the Song dynasty's Taiping Royal Prescriptions（《太平惠民合计局方》）. In the Ming and Qing dynasties， it was developed into more comprehensive formulas such as modified Bazhentang， modified Xiaoyaowan， and other formulas. In recent years， Xiaoyaowan has become a classic formula for treating many symptoms of liver depression. The Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， 2020 edition， records Xiaoyaowan and modified Xiaoyaowan. Modern clinical research has further expanded the therapeutic range of this formula. Through literature research， it is found that there are certain reports on the clinical application and quality analysis of Xiaoyaowan， but the relevant literature lacks collation so far. Therefore， relevant literature was consulted and sorted out. The paper summarized the treatment of mammary hyperplasia， depression， irregular menstruation， melasma， menopausal syndrome， and polycystic ovary syndrome with Xiaoyaowan， as well as the quality analysis of paeoniflorin， ferulic acid， and glycyrrhizinic acid of Xiaoyaowan. It is expected to lay a foundation for further research on clinical application， pharmacodynamic mechanism， and quality control of this classic formula.
ABSTRACT
ObjectiveTo explore the effects of different treatment methods of "soothing liver， invigorating spleen， soothing liver and invigorating spleen， soothing liver first and then soothing liver and invigorating spleen， as well as invigorating spleen first and then soothing liver and invigorating spleen" on liver depression combined with liver injury in rats and their action mechanisms. MethodA six-week rat model of liver depression combined with liver injury was established by restraint stress and subcutaneous injection of carbon tetrachloride （CCl4， 5.89 g·kg-1， once every three days）. At the same time， the drugs were given by gavage. Forty-eight male SD rats of clean grade were randomly divided into eight groups， namely the normal group， model group， bicyclol （0.2 g·kg-1） group， Sinisan （4.32 g·kg-1） group， Liu Junzitang （9.26 g·kg-1） group， Chaishao Liu Junzitang A （Chai A， soothing liver and invigorating spleen，13.57 g·kg-1） group， Chaishao Liu Junzitang B （Chai B， soothing liver first and then soothing liver and invigorating spleen， 13.57 g·kg-1） group， and Chaishao Liu Junzitang C （Chai C， invigorating spleen first and then soothing liver and invigorating spleen， 13.57 g·kg-1） group， with six rats in each group. The pathological changes in liver and colon tissues of each group were observed under light microscope and electron microscope. The serum biochemical indexes of the liver were detected using an automatic biochemical analyzer. The relative mRNA expression levels of Takeda G protein-coupled receptor 5 （TGR5） and intestinal mucosal zona occluden-1 （ZO-1）， Occludin， and Claudin-1 in the liver and colon were detected by reverse-transcription polymerase chain reaction （RT-PCR）. The positive expression rate of proliferating cell nuclear antigen （PCNA） in the colon was detected by immunohistochemistry. ResultCompared with normal group， the model group exhibited significantly elevated serum alkaline phosphatase （ALP）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） （P<0.01）， lowered TGR5 mRNA expression in liver tissue， up-regulated TGR5 mRNA expression in the colon tissue （P<0.05，P<0.01）， and down-regulated ZO-1， Occludin， and tight junction protein-1 (Claudin-1) mRNA expression and PCNA in the colon tissue （P<0.01）. Compared with the model group， bicyclol and Chai C remarkably decreased the levels of serum ALP， ALT， AST， TBIL， and DBIL （P<0.05，P<0.01）， while Liu Junzitang， Chai A， Chai B， and Chai C significantly up-regulated the TGR5 mRNA expression in the liver and down-regulated its expression in the colon （P<0.01）. Bicyclol， Chai A， Chai B， and Chai C enhanced the ZO-1 and Claudin-1 mRNA expression in the colon （P<0.05，P<0.01）. Bicyclol， Sinisan， and Chai C increased PCNA expression （P<0.01）. The comparison with the Chai C group showed that the TGR5 mRNA expression in the liver and ZO-1 mRNA expression in the colon of the bicyclol and Sinisan groups were lower， whereas the TGR5 mRNA expression in the colon was higher （P<0.01）. However， the PCNA expression in the colon of the Liu Junzitang and Chai B groups declined significantly （P<0.05）. ConclusionIn the presence of liver injury， invigorating spleen first helps to relieve the liver injury， and the efficacy of "spleen-invigorating" therapy in increasing the intestinal mucosal tight junction proteins and improving the gastrointestinal function is related to its activation of TGR5 to improve the intestinal mucosal barrier function， promote the renewal of intestinal stem cells， and drive the regeneration after injury.
ABSTRACT
Objective: To investigate the mechanism of lipid metabolism disorders in Kupffer cells (KCs) of non-alcoholic fatty liver disease (NAFLD) rats mediated by LXRα-SREBP-1c pathway and the interference of soothing liver and invigorating spleen recipe (SLISR) on it. Methods: SD male rats were randomly divided into five groups: normal, model, soothing liver recipe (SLR), invigorating spleen recipe (ISR), and soothing liver and invigorating spleen recipe (SLISR) groups. The rats in treatment groups were administered for 8 weeks. The liver tissue was stained with H&E and oil red O. The levels of hepatic lipid and blood lipid were measured by biochemical analyzer. KCs were isolated from the livers of rats to evaluate the expression of LXRα, SREBP-1C, and FAS mRNA by real-time fluorescence quantitative PCR tests; LXRα, SREBP-1C, and FAS proteins were measured by Western blotting. Results: The H&E and oil red O staining results showed that the model rats successfully reproduced typical pathogenetic and histopathological features of NAFLD. The levels of hepatic lipid and blood lipid in the model rats were dramatically increased. Compared with the model group, the values of hepatic lipid and blood lipid in the treatment groups were significantly ameliorated (P < 0.05, 0.01). The yields of purified KCs from each rat were 2×107-3×107. The viability of KCs was higher than 95%, with the purity over 90.18%. Compared with the model group, the expression of LXRα, SREBP-1C, and FAS mRNA and proteins was decreased in all treatment groups, especially in the SLR group (P < 0.05). Conclusion: SLISR may protect liver against injury included by lipid metabolism disorders in KCs through LXRα/SREBP-1c signaling pathway, which may be an important mechanism for the prevention and treatment of NAFLD.