Evaluating the Pharmacological Mechanism of Chinese Medicine Si-Wu-Tang through Multi-Level Data Integration

Si-Wu-Tang (SWT) is a Traditional Chinese Medicine (TCM) formula widely used for the treatments of gynecological diseases. To explore the pharmacological mechanism of SWT, we incorporated microarray data of SWT with our herbal target database TCMID to analyze the potential activity mechanism of SWT''s herbal ingredients and targets. We detected 2,405 differentially expressed genes in the microarray data, 20 of 102 proteins targeted by SWT were encoded by these DEGs and can be targeted by 2 FDA-approved drugs and 39 experimental drugs. The results of pathway enrichment analysis of the 20 predicted targets were consistent with that of 2,405 differentially expressed genes, elaborating the potential pharmacological mechanisms of SWT. Further study from a perspective of protein-protein interaction (PPI) network showed that the predicted targets of SWT function cooperatively to perform their multi-target effects. We also constructed a network to combine herbs, ingredients, targets and drugs together which bridges the gap between SWT and conventional medicine, and used it to infer the potential mechanisms of herbal ingredients. Moreover, based on the hypothesis that the same or similar effects between different TCM formulae may result from targeting the same proteins, we analyzed 27 other TCM formulae which can also treat the gynecological diseases, the subsequent result provides additional insight to understand the potential mechanisms of SWT in treating amenorrhea. Our bioinformatics approach to detect the pharmacology of SWT may shed light on drug discovery for gynecological diseases and could be utilized to investigate other TCM formulae as well.     

Traditional Chinese herbal medicine at the forefront battle against COVID-19: Clinical experience and scientific basis

BackgroundThroughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics’ infections, and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy.ApproachWe conducted conduct a systematic survey of various TCM herbal preparations used in Wuhan and to review their efficacy, according to the published clinical data; and, secondly, to find the most popular herbs used in these preparations and look into the opportunity of future research in the isolation and identification of bioactive natural products for fighting COVID-19.ResultsAlthough bioactive natural products in these herbal preparations may have direct antiviral activities, TCM employed for fighting epidemic infections was primarily based on the TCM theory of restoring the balance of the human immune system, thereby defeating the viral infection indirectly. In addition, certain TCM teachings relevant to the meridian system deserve better attention. For instance, many TCM herbal preparations target the lung meridian, which connects the lung and large intestine. This interconnection between the lung, including the upper respiratory system, and the intestine, may explain why certain TCM formulae showed excellent relief of lung congestion and diarrhea, two characteristics of COVID-19 infection.ConclusionThere is good reason for us to learn from ancient wisdom and accumulated clinical experience, in combination with cutting edge science and technologies, to fight with the devastating COVID-19 pandemic now and emerging new coronaviruses in the future.     

An integrated approach for inference and mechanistic modeling for advancing drug development

An important challenge facing researchers in drug development is how to translate multi-omic measurements into biological insights that will help advance drugs through the clinic. Computational biology strategies are a promising approach for systematically capturing the effect of a given drug on complex molecular networks and on human physiology. This article discusses a two-pronged strategy for inferring biological interactions from large-scale multi-omic measurements and accounting for known biology via mechanistic dynamical simulations of pathways, cells, and organ- and tissue level models. These approaches are already playing a role in driving drug development by providing a rational and systematic computational framework.     

Metabolite identification strategy of non-targeted metabolomics and its application for the identification of components in Chinese multicomponent medicine Abelmoschus manihot L.

Identification of multicomponent in traditional Chinese medicine (TCM) is complex and time-consuming. The inspection of the full-scan mass chromatograms was usually performed manually, which is labor-intensive. It is difficult to distinguish low response signals from complex chemical background. Furthermore, this process is typically based on earlier knowledge of the chemical composition of TCM, and those molecules that have not been characterized earlier were thus ignored. In this paper, a strategy using UPLC-MS combined with pattern recognition analysis was developed to simplify and quicken the identification of multicomponent in Abelmoschus manihot (L.) Medik. First, complex signals obtained by UPLC-MS were processed using automated data mining algorithm and further processed with multivariate chemometric methods. Multicomponent in Abelmoschus manihot L. can be clearly displayed in S- and VIP-plot. Using this method, 320 peaks which present in Abelmoschus manihot L. were detected. In the next step, accurate mass spectra of the characteristic markers acquired by QTOF MS were used to estimate their elemental formulae and enable structure identification. By searching in METLIN database, 41 components were tentatively identified in Abelmoschus manihot L. Our results showed that UPLC-MS based-pattern recognition analysis approach can be used to quickly identify TCM multicomponent and for standardization of herbal preparations.     

A survey of web resources and tools for the study of TCM network pharmacology

Background: Traditional Chinese medicine (TCM) treats diseases in a holistic manner, while TCM formulae are multi-component, multi-target agents at the molecular level. Thus there are many parallels between the key ideas of TCM pharmacology and network pharmacology. These years, TCM network pharmacology has developed as an interdisciplinary of TCM science and network pharmacology, which studies the mechanism of TCM at the molecular level and in the context of biological networks. It provides a new research paradigm that can use modern biomedical science to interpret the mechanism of TCM, which is promising to accelerate the modernization and internationalization of TCM. Results: In this paper we introduce state-of-the-art free data sources, web servers and softwares that can be used in the TCM network pharmacology, including databases of TCM, drug targets and diseases, web servers for the prediction of drug targets, and tools for network and functional analysis. Conclusions: This review could help experimental pharmacologists make better use of the existing data and methods in their study of TCM.     

Potential biomarkers in mouse myocardium of doxorubicin-induced cardiomyopathy: a metabonomic method and its application

Background

Doxorubicin (DOX) is one of the most potent antitumor agents available; however, its clinical use is limited because of the risk of severe cardiotoxicity. Though numerous studies have ascribed DOX cardiomyopathy to specific cellular pathways, the precise mechanism remains obscure. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against DOX-induced cardiomyopathy. However, its action mechanisms are not well known due to its complex components.

Methodology/Principal Findings

A tissue-targeted metabonomic method using gas chromatography–mass spectrometry was developed to characterize the metabolic profile of DOX-induced cardiomyopathy in mice. With Elastic Net for classification and selection of biomarkers, twenty-four metabolites corresponding to DOX-induced cardiomyopathy were screened out, primarily involving glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism. With these altered metabolic pathways as possible drug targets, we systematically analyzed the protective effect of TCM SND, which showed that SND administration could provide satisfactory effect on DOX-induced cardiomyopathy through partially regulating the perturbed metabolic pathways.

Conclusions/Significance

The results of the present study not only gave rise to a systematic view of the development of DOX-induced cardiomyopathy but also provided the theoretical basis to prevent or modify expected damage.     

Systematic exploration of Astragalus membranaceus and Panax ginseng as immune regulators: Insights from the comparative biological and computational analysis

BackgroundImmune system plays a decisive role for defending various pathogenic microorganisms. Astragalus membranaceus (AM) and Panax ginseng (PG) are two tonic herbs used in traditional Chinese medicine (TCM) as immune booster and help to control diseases with their healthy synergistic effect on immune system.PurposeThis study was aimed to investigate the promote effect and molecular mechanisms of AM and PG on immune system as booster and to control the target diseases using animal and computational systematic study.MethodsComputational models including absorption, distribution, metabolism, and elimination (ADME) with weighted ensemble similarity (WES) algorithm-based models and ClueGo network analysis were used to find the potential bioactive compounds targets and pathways, which were responsible for immune regulation. Viscera index analysis, proliferation activity of splenic lymphocytes and cytotoxic activity of NK cells assays were performed to validate the effect of AM and PG on immune system of long-term administrated mice. Metabonomic study of mice plasma was conducted to investigate effect of AM and PG on the endogenous metabolic perturbations, together with correlation analysis.ResultsAM and PG simultaneously showed the ability to strengthen the immune system function including enhancement of spleen and thymus index, proliferation of splenic lymphocytes and cytotoxic activity of NK cells. Besides, the different molecular mechanisms of AM and PG on immune regulation were also investigated by analyzing the potential bioactive compounds, enzymes actions and pathways. Quercetin, formononetin and kaempferol were the main immune-related compounds in AM, while ginsenoside Ra1, ginsenoside Rh1 and kaempferol in PG. About 10 target proteins were found close to immune regulation, including acetylcholinesterase (ACHE, common target in AM and PG), sphingosine kinase 1(SPHK1), cytidine deaminase (CDA), and Choline O-acetyltransferase (CHAT). Glycerophospholipid metabolism was regulated in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were considered as the special pathway in AM groups. Energy metabolism and glycerolipid metabolism were the special pathways in PG groups.ConclusionA novel comprehensive molecular mechanism analysis method was established and applied to clarify the scientific connotation of AM and PG as immune regulation, with similar herbal tonic effect provided in clinical practice of TCM, which can provide a new line of research for drug development (immune booster) using AM and PG.     

Coptidis rhizome and Si Jun Zi Tang Can Prevent Salmonella enterica Serovar Typhimurium Infection in Mice

Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and animals. Traditional Chinese Medicine (TCM) has been used to improve gastrointestinal dysfunction and to modify the immune response to inflammation for centuries. This study used six herbal plants and four TCM formulae to rate their efficacy in preventing S. Typhimurium infection via mouse model. Minimum bactericidal concentration (MBC) of Coptidis rhizome (CR) against the reference strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of other herbal extracts and formulae on Salmonella Typhimurium strains were above 50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT) could significantly decrease the bacterial load in organs and blood after being challenged, along with body weight loss due to the infection. CR and SJZT alleviated infection-induced interferon-gamma levels in the serum and tissues, and tumor necrosis factor-alpha (TNF-α) levels in intestinal tissues. CR and SJZT serum metabolites could suppress S. Typhimurium invasion and TNF-α expression in RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine, ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading macrophages. CR and SJZT has shown potential in preventing S. Typhimurium infection through the regulation of the immune response.     

Cochrane systematic reviews of Chinese herbal medicines: an overview

Objectives

Our study had two objectives: a) to systematically identify all existing systematic reviews of Chinese herbal medicines (CHM) published in Cochrane Library; b) to assess the methodological quality of included reviews.

Methodology/Principal Findings

We performed a systematic search of the Cochrane Database of Systematic Reviews (CDSR, Issue 5, 2010) to identify all reviews of CHM. A total of fifty-eight reviews were eligible for our study. Twenty-one of the included reviews had at least one Traditional Chinese Medicine (TCM) practitioner as its co-author. 7 reviews didn''t include any primary study, the remaining reviews (n = 51) included a median of 9 studies and 936 participants. 50% of reviews were last assessed as up-to-date prior to 2008. The questions addressed by 39 reviews were broad in scope, in which 9 reviews combined studies with different herbal medicines. For OQAQ, the mean of overall quality score (item 10) was 5.05 (95% CI; 4.58-5.52). All reviews assessed the methodological quality of primary studies, 16% of included primary studies used adequate sequence generation and 7% used adequate allocation concealment. Of the 51 nonempty reviews, 23 reviews were reported as being inconclusive, while 27 concluded that there might be benefit of CHM, which was limited by the poor quality or inadequate quantity of included studies. 58 reviews reported searching a median of seven electronic databases, while 10 reviews did not search any Chinese database.

Conclusions

Now CDSR has included large numbers of CHM reviews, our study identified some areas which could be improved, such as almost half of included reviews did not have the participation of TCM practitioners and were not up-to-date according to Cochrane criteria, some reviews pooled the results of different herbal medicines and ignored the searching of Chinese databases.     

Synergism and Rules from Combination of Baicalin,Jasminoidin and Desoxycholic acid in Refined Qing Kai Ling for Treat Ischemic Stroke Mice Model

Refined Qing-Kai-Ling (QKL), a modified Chinese medicine, consists of three main ingredients (Baicalin, Jasminoidin and Desoxycholic acid), plays a synergistic effect on the treatment of the acute stage of ischemic stroke. However, the rules of the combination and synergism are still unknown. Based on the ischemic stroke mice model, all different kinds of combination of Baicalin, Jasminoidin, and Desoxycholic acid were investigated by the methods of neurological examination, microarray, and genomics analysis. As a result, it confirmed that the combination of three drugs offered a better therapeutical effect on ischemic stroke than monotherapy of each drug. Additionally, we used Ingenuity pathway Analysis (IPA) and principal component analysis (PCA) to extract the dominant information of expression changes in 373 ischemia-related genes. The results suggested that 5 principal components (PC1-5) could account for more than 95% energy in the gene data. Moreover, 3 clusters (PC1, PC2+PC5, and PC3+PC4) were addressed with cluster analysis. Furthermore, we matched PCs on the drug-target networks, the findings demonstrated that Baicalin related with PC1 that played the leading role in the combination; Jasminoidin related with PC2+PC5 that played a compensatory role; while Desoxycholic acid had the least performance alone which could relate with PC3+PC4 that played a compatible role. These manifestations were accorded with the principle of herbal formulae of Traditional Chinese Medicine (TCM), emperor-minister-adjuvant-courier. In conclusion, we firstly provided scientific evidence to the classic theory of TCM formulae, an initiating holistic viewpoint of combination therapy of TCM. This study also illustrated that PCA might be an applicable method to analyze the complicated data of drug combination.     

Metabonomic profiles delineate the effect of traditional Chinese medicine sini decoction on myocardial infarction in rats

Background

In spite of great advances in target-oriented Western medicine for treating myocardial infarction (MI), it is still a leading cause of death in a worldwide epidemic. In contrast to Western medicine, Traditional Chinese medicine (TCM) uses a holistic and synergistic approach to restore the balance of Yin-Yang of body energy so the body''s normal function can be restored. Sini decoction (SND) is a well-known formula of TCM which has been used to treat MI for many years. However, its holistic activity evaluation and mechanistic understanding are still lacking due to its complex components.

Methodology/Principal Findings

A urinary metabonomic method based on nuclear magnetic resonance and ultra high-performance liquid chromatography coupled to mass spectrometry was developed to characterize MI-related metabolic profiles and delineate the effect of SND on MI. With Elastic Net for classification and selection of biomarkers, nineteen potential biomarkers in rat urine were screened out, primarily related to myocardial energy metabolism, including the glycolysis, citrate cycle, amino acid metabolism, purine metabolism and pyrimidine metabolism. With the altered metabolism pathways as possible drug targets, we systematically analyze the therapeutic effect of SND, which demonstrated that SND administration could provide satisfactory effect on MI through partially regulating the perturbed myocardial energy metabolism.

Conclusions/Significance

Our results showed that metabonomic approach offers a useful tool to identify MI-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating MI.     

Computational Design of Plant-Based Antistress Agents Targeting Nociceptin Receptor

Stress is the body's reaction to the challenges it faces, and it produces a multitude of chemical molecules known as stressors as a result of these reactions. It's also a misalignment of the sympathetic and parasympathetic nervous systems causing changes in a variety of physiological reactions and perhaps leading to stress disorders. The reduction in neurotransmitter & neurohormonal hormones is mainly governed by the nociceptin receptor as G-protein coupled receptor and increased the level of reactive oxygen species. Various synthetic medicines that target nociceptin receptors were utilized to reduce the effects of stress but they come up with a variety of side effects. Because of the widespread utilization and renewed interest in medicinal herbal plants considered to be alternative antistress therapy. Our present work is an approach to decipher the molecular nature of novel herbal leads by targeting nociceptin receptor, under which herbal compounds were screened and validated through in-silico methods. Among screened leads, withanolide-B showed stable association in the active site of the nociceptin receptor as an antistress agent with no side effects. Furthermore, the selected lead was also evaluated for stability by molecular dynamic stimulation as well as for pharmacokinetics and toxicity profile. It has been concluded stable conformation of withanolide-B without presence of any major toxic effects. As a result, the in silico molecular docking technique is a highly successful method for selecting a prospective herbal lead molecule with respect to a specific target, and future research can pave the way for further exploration in the drug development field.     

Chinese Herbal Therapy and Western Drug Use,Belief and Adherence for Hypertension Management in the Rural Areas of Heilongjiang Province,China

Background

Traditional Chinese medicine (TCM) including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China.

Methodology and Principal Findings

This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users). When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy.

Conclusions and Significance

Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.     

Metabolic Profiling Provides a System Understanding of Hypothyroidism in Rats and Its Application

Background

Hypothyroidism is a chronic condition of endocrine disorder and its precise molecular mechanism remains obscure. In spite of certain efficacy of thyroid hormone replacement therapy in treating hypothyroidism, it often results in other side effects because of its over-replacement, so it is still urgent to discover new modes of treatment for hypothyroidism. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against hypothyroidism. However, its holistic effect assessment and mechanistic understanding are still lacking due to its complex components.

Methodology/Principal Findings

A urinary metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry was employed to explore global metabolic characters of hypothyroidism. Three typical hypothyroidism models (methimazole-, propylthiouracil- and thyroidectomy-induced hypothyroidism) were applied to elucidate the molecular mechanism of hypothyroidism. 17, 21, 19 potential biomarkers were identified with these three hypothyroidism models respectively, primarily involved in energy metabolism, amino acid metabolism, sphingolipid metabolism and purine metabolism. In order to avert the interference of drug interaction between the antithyroid drugs and SND, the thyroidectomy-induced hypothyroidism model was further used to systematically assess the therapeutic efficacy of SND on hypothyroidism. A time-dependent recovery tendency was observed in SND-treated group from the beginning of model to the end of treatment, suggesting that SND exerted a recovery effect on hypothyroidism in a time-dependent manner through partially regulating the perturbed metabolic pathways.

Conclusions/Significance

Our results showed that the metabonomic approach is instrumental to understand the pathophysiology of hypothyroidism and offers a valuable tool for systematically studying the therapeutic effects of SND on hypothyroidism.     

中医药的抗炎机制在治疗肝纤维化中的作用

肝脏是人体腹腔内最大的实体器官,对维持机体的基本生理功能起着至关重要的作用。肝脏疾病是威胁人类健康的常见病多发病。全球约有10%人口受到不同程度的肝脏疾病的危害,其中,肝纤维化往往成为这些疾病的晚期病理特征。由于肝纤维化的发病机制复杂,尚无有效的合成类药物能够治疗肝纤维化。中药治疗肝纤维化具有多靶点和副作用小的优势。本文综述了肝纤维化的病理特征与诱发炎症的关系,讨论了中药治疗肝纤维化的单味中药、传统配方及其化学活性成分的抗炎症机制。     

In vitro and in vivo assessment of herb drug interactions

Herbal products contain several chemicals that are metabolized by phase 1 and phase 2 pathways and also serve as substrates for certain transporters. Due to their interaction with these enzymes and transporters there is a potential for alteration in the activity of drug metabolizing enzymes and transporters in presence of herbal components. Induction and inhibition of drug metabolizing enzymes and transporters by herbal component has been documented in several in vitro studies. While these studies offer a system to determine the potential for a herbal component to alter the pharmacokinetics of a drug, they cannot always be used to predict the magnitude of any potential effect in vivo. In vivo studies are the ultimate way to determine the clinical importance of herb drug interactions. However, lack of content uniformity and lack of documentation of the bioavailability of herbal components makes even in vivo human studies difficult to interpret as the effect may be product specific. It appears that St. John's wort extract is probably one of the most important herbal product that increases the metabolism and decreases the efficacy of several drugs. Milk thistle on the other hand appears to have minimal effect on phase 1 pathways and limited data exists for phase 2 pathways and transporter activity in vivo. Further systematic studies are necessary to assess the significance of herb drug interactions.     

Disruption of a ∼23–24 nucleotide small RNA pathway elevates DNA damage responses in Tetrahymena thermophila

Endogenous RNA interference (RNAi) pathways regulate a wide range of cellular processes in diverse eukaryotes, yet in the ciliated eukaryote, Tetrahymena thermophila, the cellular purpose of RNAi pathways that generate ∼23–24 nucleotide (nt) small (s)RNAs has remained unknown. Here, we investigated the phenotypic and gene expression impacts on vegetatively growing cells when genes involved in ∼23–24 nt sRNA biogenesis are disrupted. We observed slower proliferation and increased expression of genes involved in DNA metabolism and chromosome organization and maintenance in sRNA biogenesis mutants RSP1Δ, RDN2Δ, and RDF2Δ. In addition, RSP1Δ and RDN2Δ cells frequently exhibited enlarged chromatin extrusion bodies, which are nonnuclear, DNA-containing structures that may be akin to mammalian micronuclei. Expression of homologous recombination factor Rad51 was specifically elevated in RSP1Δ and RDN2Δ strains, with Rad51 and double-stranded DNA break marker γ-H2A.X localized to discrete macronuclear foci. In addition, an increase in Rad51 and γ-H2A.X foci was also found in knockouts of TWI8, a macronucleus-localized PIWI protein. Together, our findings suggest that an evolutionarily conserved role for RNAi pathways in maintaining genome integrity may be extended even to the early branching eukaryotic lineage that gave rise to Tetrahymena thermophila.     

In silico toxicity studies of traditional Chinese herbal medicine: A mini review

With the availability of public databases that store compound-target/compound-toxicity information, and Traditional Chinese medicine (TCM) databases, in silico approaches are used in toxicity studies of TCM herbal medicine. Here, three in silico approaches for toxicity studies were reviewed, which include machine learning, network toxicology and molecular docking. For each method, its application and implementation e.g., single classifier vs. multiple classifier, single compound vs. multiple compounds, validation vs. screening, were explored. While these methods provide data-driven toxicity prediction that is validated in vitro and/or in vivo, it is still limited to single compound analysis. In addition, these methods are limited to several types of toxicity, with hepatotoxicity being the most dominant. Future studies involving the testing of combination of compounds on the front end i.e., to generate data for in silico modeling, and back end i.e., validate findings from prediction models will advance the in silico toxicity modeling of TCM compounds.     

Network pharmacology and pharmacokinetics integrated strategy to investigate the pharmacological mechanism of Xianglian pill on ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic inflammatory bowel disease with high morbidity, which leads to poor quality of life. The Xianglian pill (XLP) is a classical Chinese patent medicine and has been clinically proven to be an effective treatment for UC.PurposeThe pharmacological mechanism of the key bioactive ingredients of XLP for the treatment of UC was investigated by a network pharmacology and pharmacokinetics integrated strategy.Study design and methodsNetwork pharmacology was used to analyze the treatment effect of nine quantified XLP ingredients on UC. Key pathways were enriched and analyzed by protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses. The effect of XLP on Th17 cell differentiation was validated using a mouse model of UC. The binding of nine compounds with JAk2, STAT3, HIF-1α, and HSP90AB1 was assessed using molecular docking. A simple and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantification of nine ingredients from XLP in plasma and applied to a pharmacokinetic study following oral administration.ResultsNine compounds of XLP, including coptisine, berberine, magnoflorine,berberrubine, jatrorrhizine, palmatine, evodiamine, rutaecarpine, and dehydrocostus lactone, were detected. Network pharmacology revealed 50 crossover genes between the nine compoundsand UC. XLP treats UC mainly by regulating key pathways of the immune system, including Th17 cell differentiation, Jak-Stat, and PI3K-Akt signaling pathways. An in vivo validation in mice found that XLP inhibits Th17 cell differentiation by suppressing the Jak2-Stat3 pathway, which alleviates mucosal inflammation in UC. Molecular docking confirmed that eight compounds are capable of binding with JAk2, HIF-1α, and HSP90AB1, further confirming the inhibitory effect of XLP on the Jak2-Stat3 pathway. Moreover, apharmacokinetic study revealed that the nine ingredients of XLP are exposed in the plasma and colon tissue, which demonstrates its pharmacological effect on UC.ConclusionThis study evaluates the clinical treatment efficacy of XLP for UC. The network pharmacology and pharmacokinetics integrated strategy evaluation paradigm is efficient in discovering the key pharmacological mechanism of herbal formulae.