Rapid Investigation and Screening of Bioactive Components in Simo Decoction via LC-Q-TOF-MS and UF-HPLC-MD Methods.

Simo decoction (SMD), as a traditional medicine, is widely used in the treatment of gastrointestinal dysmotility in China. In this study, a combined method of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and ultrafiltration high-performance liquid chromatography molecular docking (UF-HPLC-MD) was efficiently employed to identify and screen bioactive ingredients in SMD. Ninety-four major constituents were identified or tentatively characterized by comparing their retention times and mass spectra with standards or literature data by using LC-Q-TOF-MS, and the ascription of those compounds were classified for the first time. Among them, 13 bioactive ingredients, including norisoboldine, eriocitrin, neoeriocitrin, narirutin, hesperidin, naringin, neohesperidin, hesperitin-7-O-glucoside, linderane, poncirin, costunolide, nobiletin, and tangeretin, were primarily identified as the human serum albumin (HSA) ligands at a range of docking scores from -29.7 to -40.6 kJ/mol by UF-HPLC-MD. The results indicate the systematic identification and screening of HSA ligands from Simo decoction guided by LC-Q-TOF-MS and UF-HPLC-MD represents a feasible and efficient method that could be extended for the identification and screening of other bioactive ingredients from natural medicines.

Safety and efficacy evaluation of Simo decoction and Arecae semen in herbal medicine practice.

Objective: The traditional Chinese patent medicine (TCPM), Simo decoction (Simo decoction oral solution), with its primary ingredient Arecae semen (Binglang, Areca catechu L.), known for its potential carcinogenic effects, is the subject of this study. The research aims to analyze the effectiveness and potential risks of Simo decoction, particularly as a carcinogen, and to suggest a framework for evaluating the risks and benefits of other herbal medicines. Methods: The study is based on post-marketing research of Simo decoction and Arecae semen. It utilized a wide range of sources, including ancient and modern literature, focusing on the efficacy and safety of Simo decoction. The research includes retrospective data on the sources, varieties, and toxicological studies of Arecae semen from databases such as Pubmed, Clinical Trials, Chinese Clinical Trial Registry, China National Knowledge Infrastructure, WHO-UMC Vigibase, and China National Center for ADR Monitoring. Results: Common adverse drug reactions (ADRs) associated with Simo decoction include skin rash, nausea, vomiting, abdominal pain, and diarrhea. However, no studies exist reporting the severe ADRs, such as carcinogenic effects. Arecae semen is distributed across approximately 60 varieties in tropical Asia and Australia. According to the WHO-UMC Vigibase and the National Adverse Drug Reaction Monitoring System databases, there are currently no reports of toxicity related to Arecae semen in the International System for Classification of ADRs (ISCR) or clinical studies. Conclusion: Risk-benefit analysis in TCPM presents more challenges compared to conventional drugs. The development of a practical pharmacovigilance system and risk-benefit analysis framework is crucial for marketing authorization holders, researchers, and regulatory bodies. This approach is vital for scientific supervision and ensuring the safety and efficacy of drug applications, thus protecting public health.

Combination of Simo Decoction and Golden Bifid alleviates functional dyspepsia through a mechanism involving intestinal microbiota and short-chain fatty acids.

BACKGROUND AND STUDY AIMS: The integration of traditional Chinese medicine and Western medicine holds promise for the treatment of gastrointestinal disorders, which are influenced by intestinal microbiota and metabolites. This study reports a possible mechanism for the combination of Simo Decoction and Golden Bifid in functional dyspepsia (FD) by regulating intestinal microbiota and short-chain fatty acids (SCFAs). PATIENTS AND METHODS: A mouse model of food stagnation was constructed and treated with Simo Decoction combined with different concentrations of Golden Bifid. Meta-genomics sequencing was conducted to analyze the cecum contents of the mice. Following analyses of the composition and abundance of intestinal microbiota, gas chromatography-mass spectrometry was performed to measure SCFAs in the colonic content of mice. Finally, ELISA was utilized to determine the levels of pro-inflammatory factors in the duodenal mucosa of mice and the infiltration of eosinophils in the duodenum was observed by immunohistochemical staining. RESULTS: Combination of Simo Decoction and Golden Bifid more significantly alleviated dyspepsia in mice with food stagnation compared with Simo Decoction alone. The optimal ratio of combined treatment was 0.0075 mL/g (body weight) Simo Decoction and 0.0032 mg/g (body weight) Golden Bifid. The combined treatment increased the abundance of Bifidobacterium and Bacteroides in the intestine. The levels of SCFAs in the colonic contents of mice were increased after the combined treatment, contributing to diminished pro-inflammatory factors in the duodenal mucosa and reduced eosinophil infiltration. CONCLUSION: Combination of Simo Decoction and Golden Bifid increases the abundance of Bacteroides and Bifidobacterium and promotes the production of SCFAs, which is instrumental for alleviation of FD.

Simo decoction curing spleen deficiency constipation was associated with brain-bacteria-gut axis by intestinal mucosal microbiota.

Background: Simo decoction (SMD) is a traditional prescription for treating gastrointestinal diseases. More and more evidences prove that SMD can treat constipation by regulating intestinal microbiota and related oxidative stress indicators, but the specific mechanism is still unclear. Methods: A network pharmacological analysis was used to predict the medicinal substances and potential targets of SMD to alleviate constipation. Then, 15 male mice were randomly divided into normal group (MN group), natural recovery group (MR group), and SMD treatment group (MT group). Constipation model mice were constructed by gavage of Folium sennae decoction and control of diet and drinking water, and SMD was used for intervention after successful modeling. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), superoxide dismutase (SOD), malondialdehyde (MDA), and fecal microbial activities were measured, and the intestinal mucosal microbiota was sequenced. Result: Network pharmacology analysis showed that a total of 24 potential active components were obtained from SMD, and 226 target proteins were obtained after conversion. Meanwhile, we obtained 1,273 and 424 disease-related targets in the GeneCards database and the DisGeNET database, respectively. After combination and deduplication, the disease targets shared 101 targets with the potential active components of SMD. When the mice were intervened with SMD, the 5-HT, VIP, MDA, SOD content, and microbial activity in MT group were close to MN group, and Chao 1 and ACE in MT group were significantly higher than that in MR group. In the Linear discriminant analysis Effect Size (LEfSe) analysis, the abundance of beneficial bacteria such as Bacteroides, Faecalibacterium, Alistipes, Subdoligranulum, Lactiplantibacillus, and Phascolarctobacterium in MT group increased. At the same time, there were some associations between microbiota and brain-gut peptides and oxidative stress indicators. Conclusion: SMD can promote intestinal health and relieve constipation through brain-bacteria-gut axis associating with intestinal mucosal microbiota and alleviate oxidative stress.

Simo decoction versus domperidone suspension for post-pyloric spiral nasoenteric tube placement: A multicenter, randomized, non-inferiority trial.

BACKGROUND & AIMS: Leveraging prokinetics to facilitate trans-pyloric migration is a conventional strategy. However, due to restrictions on the use of domperidone suspension, oral prokinetics is relatively modest. The study aims to assess the effectiveness of simo decoction as an alternative to domperidone suspension in facilitating post-pyloric placement of spiral nasoenteric tubes. METHODS: A prospective, open-label, parallel, and non-inferiority randomized controlled trial was performed involving critically ill adults in 6 university hospitals in China between September 2017 and May 2019. Patients were randomly assigned to receive either simo decoction 20 ml q8h, or domperidone suspension 20 mg/20 ml q6h for 24 h. The primary outcome was procedure success defined as post-pyloric placement (spiral nasoenteric tubes reached the first portion of the duodenum or beyond confirmed by abdominal X-ray 24 h after tube insertion). RESULTS: Of 268 patients assessed for eligibility, 224 patients were enrolled and randomly assigned to the simo decoction group or the domperidone suspension group (n = 112 per group). The success rate of post-pyloric placement was 41.1% (46/112) in the simo decoction group, as compared with 47.3% (53/112) in the domperidone suspension group (a risk difference of -6.3%, 95% CI, -19.2% to 6.7%, adjusted risk difference -3.7%, 95% CI -16.3% to 9.0%), in the intention-to-treat analysis, crossing the prespecified margin of -10% for non-inferiority. There were no differences between groups in the success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond) and proximal jejunum placement, the incidences of any adverse events, length of ICU stay or mortality in ICU. CONCLUSIONS: Non-inferiority of simo decoction to domperidone suspension was not confirmed in facilitating post-pyloric placement of spiral nasoenteric tubes. Registration: The trial was registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn (registration number ChiCTR-INR-17011311).

Clinical Study on Simo Decoction for Treatment of Feeding Intolerance of Near Term Infants / 中国中医药信息杂志

Objective To study the clinical efficacy and safety of Simo Decoction for the treatment of feeding intolerance of near term infants; To explore the value of increase of time averaged mean velocity (TAMV) in the superior mesenteric artery. Methods Totally 85 patients were randomly divided into control group (41 cases) and observation group (44 cases). Both two group were given comprehensive treatment and feeding regulation, lasted for 7 d. The observation group was given Simo Decoction on the basis of the control group, 1 mL/kg each time, 3 times a day, orally or nasal feeding, lasted for 2 days. After the treatment, no gastric retention time, vomiting ceased time, total enteral nutrition time, and hospitalization time were compared, and the total TCM syndrome scores and TAMV increase were observed. Clinical efficacy was evaluated and safety indexes were monitored. Results No gastric retention time, vomiting ceased time, total enteral nutrition time and hospitalization time in the observation group were shorter than the control group (P<0.05). Compared with before treatment, the total TCM syndrome scores in the two groups decreased after treatment (P<0.05); After treatment, the total TCM syndrome scores in the observation group were lower than those in the control group (P<0.05). The total effective rate was 86.36% (38/44) in the observation group and 68.29% (28/41) in the control group. The observation group was significantly better than the control group (P<0.05); After treatment, the TAMV increase in the observation group was higher than that in the control group (P<0.05). No adverse reactions occurred in both groups. Conclusion Simo Decoction can improve the symptoms and shorten the time of hospitalization in the treatment of feeding intolerance of near term infants, with confirmed efficacy and no obvious adverse reactions, which can be prejudged and monitored by monitoring TAMV increase.

Effect of simo decoction combined with mannitol on intestinal preparation before magnetically guided capsule endoscopy examination / 上海交通大学学报（医学版）

Objective · To investigate the effects of simo decoction combined with mannitol on the intestinal preparation of magnetically guided capsule endoscopy (MGCE). Methods · A total of 120 patients were enrolled in this randomized controlled trial and randomly divided into two groups according to the random number table. The observation group (n=60) was pretreated with simo decoction 20 mL each time, 3 times a day combined with mannitol 500 mL for oral administration before MGCE examination, while control group (n=60) only was done with mannitol 500 mL for oral administration. Then the intestinal cleanliness and occurrence of adverse reaction were observed. Results · The intestine bubbles in observation group were less than that of control group based on evaluation criteria (Z=-1.976, P=0.048), and the intestine juices in observation group were also less than control group (Z=-2.489,P=0.013) suggesting that the intestinal cleanliness in observation group was superior to control group. Simultaneously, the score of nausea and vomiting in observation group was lower than control group according to the evaluation criteria (Z=-2.215, P=0.027), and abdominal pain, distension and anal stenosis in observation group were less than control group (Z=-2.158, P=0.031), meanwhile, the overall incidences of adverse reaction were 8.33% and 36.67%, respectively (χ2=13.811, P=0.000) , all of which implied that the occurrence of adverse reaction was lower in observation group compared to control group. Conclusion · Simo decoction combined with mannitol could enhance intestinal cleanliness and reduce the occurrence of adverse reaction so as to improve the effect of intestinal preparation.

Observations on the Efficacy of Acupoint Application plus Simo Decoction Oral Liquid in Treating Functional Dyspepsia / 上海针灸杂志

Objective To investigate the clinical efficacy of acupoint application plus Simo decoction oral liquid in treating functional dyspepsia (FD).Method Ninety-five FD patients were randomized to a treatment group (48 cases) and a control group (47 cases).The treatment group received acupoint application plus Simo decoction oral liquid and the control group,oral administration of omeprazole enteric-coated capsules and mosapride citrate tablets.The clinical therapeutic effects were compared between the groups after four weeks of treatment.Result After one week of treatment,the cure and marked efficacy rate and the total efficacy rate were 20.8％ and 54.2％,respectively,in the treatment group and 40.4％ and 66.0％,respectively,in the control group (P＜0.05).There was a statistically significant difference in the cure and marked efficacy rate between the two groups (P＜0.05).After four weeks of treatment,the cure and marked efficacy rate and the total efficacy rate were 81.3％ and 89.6％,respectively,in the treatment group and 61.7％ and 72.3％,respectively,in the control group.There were statistically significant differences in both the cure and marked efficacy rate and the total efficacy rate between the two groups (P＜0.05).Conclusion Acupoint application plus Simo decoction oral liquid is an effective way to treat FD.

A study on effect of traditional Chinese medicine Simo decoction on acute respiratory distress syndrome / 中国中西医结合急救杂志

Objective To investigate the effect of Simo decoction oral liquid on inflammatory in acute respiratory distress syndrome (ARDS) mouse serum and the bronchoalveolar lavage fluid (BALF) and to explore the mechanism.Methods Fifty BALB/c mice were divided into normal control group, ARDS model group, small, moderate and large dose Simo decoction oral liquid-treated groups (simplified as Simo groups) according to random number table method (n=10, in each group). The ARDS model mice were replicated by lipopolysaccharide (LPS) tracheal instillation, and the mice in normal control group were given the same amount of normal saline. Immediately after the success of modeling, the mice were gavaged with 1, 2, 4 times the equivalent dose Simo decoction oral liquid of 7.56 mL·kg-1·d-1 in small, moderate or large dose Simo groups respectively, and there was no intervention in the normal control group or ARDS model group. All the mice were sacrificed at 24 hours after the respective drug amount or normal saline was given in various groups. The lung samples were taken for histologic evaluation, and BALF and serum samples were analyzed for the tumor necrosis factor-α(TNF-α), interleukin (IL-1β, IL-6), and in the mean time the level of serum superoxide dismutase (SOD) was detected.Results The pathological observation of lung tissue showed: there was no obvious inflammatory exudation in lung tissue of mice in normal control group; the inflammatory exudation in lung tissue of mice was increased significantly, the level of TNF-α (ng/L: 1759±303 vs. 104±27, 2506±674 vs. 507±46), IL-1β(ng/L: 209±16 vs. 114±11, 7325±826 vs. 3513±498) and IL-6 (ng/L: 144±38 vs. 47±7, 126±38 vs. 15±7) in serum and BALF were significantly increased, and the content of SOD (kU/L: 40.26±2.54 vs. 50.68±3.75) in serum was significantly decreased in ARDS model group (allP < 0.05), indicating that animal model of ARDS was set up successfully. Compared with ARDS model group, in small, moderate and large dose Simo groups, the inflammation exudation in lung tissue of mouse was reduced, the levels of TNF-α, IL-1βand IL-6 in serum and BALF were reduced, and the content of SOD in serum was increased [serum: TNF-α(ng/L) was 1642±276, 1126±154, 817±102 vs. 1759±303, IL-1β(ng/L)was 198±12, 170±11, 141±13 vs. 209±16, IL-6 (ng/L) was 127±22, 82±16, 41±15 vs. 144±38, SOD (kU/L) was 42.11±1.64, 48.09±1.23 vs. 40.26±2.54; BALF: TNF-α(ng/L) was 2479±446, 1632±330, 1067±223 vs. 2506±674, IL-1β(ng/L): 6939±725, 5398±625, 4401±210 vs. 7325±826, IL-6 (ng/L): 106±30, 68±13, 34±10 vs. 126±38, allP < 0.05], showing the Simo decoction inhibiting the lung inflammation and the above levels of indexes inserum and BALF was in a dose-dependent manner, and the changes in large dose Simo group was the most significant 45.18±1.15, .Conclusions Simo decoction oral liquid can inhibit the inflammatory response of ARDS, reduce the oxidative stress and decrease the lung injury of mice with ARDS.

Effect compare of trimebutine maleate with and without Simo decoction to improve gastrointestinal function in the treatment of mice removed part of colon / 局解手术学杂志

Objective To discuss the efficacy and pharmacological mechanism of Simo decoction to assist the treatment of postoperative gastrointestinal dysfunction. Methods 200 mice (100 male and 100 female) were randomly divided into four groups (n=50). The mice of blank group were feed as normal,and the mice in the other three groups were prepared for colon postoperative gastrointestinal dysfunction model. Then,trimebutine maleate group were given trimebutine maleate while the combined group were given trimebutine maleate and simo decoction through gavage,and model group and blank group were given the same doses of distilled water. One week later,the abdominal ve-nous blood of mice was extracted and serum levels of acetylcholine ( ACH) and norepinephrine ( NE) were detected using ELISA kit. At the samd time,the gastric emptying and intestinal propulsion experiment was carried on. Results After modeling,compared with blank group, MUPA of the rest three groups were significantly decreased (P0. 05). After drug intervention,MUPA of trimebutine maleate group was significantly higher than that of model group,and MUPA of combined group was significantly higher than that of trimebutine maleate group (P<0. 05). In addition,compared with blank group,the gas-tric emptying rate,intestinal propulsion rate,serum ACH concentration and NE concentration of the rest three groups were significantly lower (P<0. 05). Compared with model group,each index of both trimebutine maleate group and combined group was increased,and combined group increased higher (P<0. 05). Conclusion Simo decoction combined trimebutine maleate has high effect to improve the level of ACH and NE of postoperative gastrointestinal dysfunction mice,which benefit to promote gastrointestinal peristalsis and may be one of its pharmaco-logical mechanisms.

Effect of Simo Decoction on Gastrointestinal Motility in Patients with Chronic Obstructive Pulmonary Disease / 胃肠病学

Background:Gastrointestinal dysmotility is frequently seen in patients with chronic obstructive pulmonary disease ( COPD). Simo Decoction is used for promoting gastrointestinal motility in clinical practice. Aims:To study the effect of Simo Decoction on gastrointestinal symptoms and motility in patients with COPD. Methods:Thirty-six patients with stable COPD in Shiyan Renmin Hospital from Sep. 2012 to Jun. 2013 were enrolled and received a 28-day course treatment of Simo Decoction oral solution,19 healthy volunteers were served as controls. All subjects were assessed with gastrointestinal symptom rating scale(GSRS). Electrogastrography was performed and levels of vasoactive intestinal peptide(VIP)and intestinal fatty acid-binding protein( I-FABP)in peripheral blood were measured. Patients with COPD were re-examined for the above-mentioned parameters after treated with Simo Decoction. Results:The baseline GSRS score and serum I-FABP level in COPD patients were significantly increased as compared with controls(P<0. 05),while the baseline serum VIP level,as well as the fasting and postprandial normal gastric slow wave percentage in COPD patients were significantly decreased(P <0. 05). After 28-day course of Simo Decoction treatment,all these parameters in COPD patients were improved as compared with those before treatment(P<0. 05),serum levels of VIP,I-FABP and normal gastric slow wave percentage were similar to those of controls. Conclusions:Simo Decoction can ameliorate the gastrointestinal symptoms and dysmotility in patients with COPD. The regulatory effect of Simo Decoction on gastrointestinal motility might be bidirectional.

Effects of Simo decoction on calcitonin gene-related peptide and ghrelin in diabetic rats / 中华消化杂志

Objective To investigate the effects of Simo decoction on ghrelin and calcitonin gene-related peptide (CGRP) in diabetic rats.Methods A total of 48 SD rats were divided into healthy control group,diabetes group (DM),DM treated with low dose Simo decoction group (DMTL),DM treated with medium dose Simo decoction group (DM-TM),DM treated with high dose Simo decoction group (DM-TH) and DM prevented with medium dose Simo decoction group (DMPM) ; there were eight rats in each group.The rats of DM group and other intervention groups were intraperitoneally injected with 1％ streptozotoein (STZ) to establish the model.The rats of healthy control group were injected with solvent.At eight weeks after the model successfully established,the rats of each intervention group were gavaged with low dose of Simo decoction (0.15 ml · kg-1 · d-1 ),medium dose of Simo decoction (1.5 ml · kg-1 · d-1 ) and high dose of Simo decoction (3.0 ml · kg-1 ·d-1 ) for two weeks; the rats of control group and DM groups were gavaged with equal volume of 0.9％NaCl.The rats of DM-PM group were gavaged with Simo decoction at 1.5 ml · kg-1 · d-1 for 10 weeks after the model successfully established.Rats were sacrificed at the end of drug intervention and gastric antrum tissues were dissociated for detecting the expression of ghrelin and CGRP by real time polymerase chain reaction (PCR).The data were analyzed by one way ANOVA and t test.Results There was no significant difference in ghrelin expression at mRNA level in gastric antrum tissues between diabetic rats and control group.However after intervened by low dose and medium dose of Simo decoction,the ghrelin expression increased (1.45 ± 0.34,1.87 ± 0.68 compared with 0.87 ±0.28,Dunnett's T3 test,P＜0.05).There was no effects of high dose Simo decoction on the expression of ghrelin in diabetic rats.There was no significant difference in ghrelin between DM-TM and DM-PM.The expression of CGRP at mRNA level in gastric antrum tissues of diabetic rats was significantly higher than that of control group (4.61 ± 1.67 compared with 1.06 ± 0.40,t =5.843,P＜0.01).There was no effects of low dose Simo decoction on CGRP expression of diabetic rats.The expression of CGRP of diabetic rats was down-regulated by medium and high dose of Simo decoction intervention.There was no significant difference in CGRP expression between DM-TM and DM-PM.Conclusions Simo decoction can promote ghrelin expression in gastric antrum of diabetic rats.The expression of CGRP in gastric antrum of diabetic rats significantly increased,but Simo decoction may down-regulate the expression of CGRP in gastric antrum of diabetic rats.

Treatment of senile constipation with Simo Decoction / 国际中医中药杂志

Objective To study the effect of Simo Decoction on senile constipation. Methods A total of 109 cases with senile constipation were randomly recruited into a control group (49 case) and a treatment group (60 case). The control group was treated with Dangguihuilong pill, while the treatment group was additionally treated with Simo Decoction on that basis.Results The total effective rate was 93.33% and 79.59% in the treatment group and the control group respectively, showing statistical difference (x2=22.586, P＜0.01). Conclusion It was effective to treat senile constipation with Simo Decoction.

Clinical efficacy of Simo Tang on functional dyspepsia with syndrome of incoordination between the liver and spleen and its effect on motilin and substance P in plasma / 中华中医药杂志

0.05). However,Simo Decoction can ameliorate the symptoms,such as epigastric pain,early satiety,etc.,better than Domperidone tablets(P