Shang Han Lun Research Articles

Neural Circuit Mechanisms of Sinisan formula for the Treatment of adolescent Depression: prefrontal cortex to dorsal raphe nucleus

Ethnopharmacological relevanceSinisan formula (SNSF), documented in the classic books Shanghan Lun, is known for its ability to regulate liver-qi and treat depression. However, its underlying mechanism, particularly its effects on dynamic real-time neuron activity and circuits remains to be fully elucidated. Aim of the studyThis study aimed to investigate the antidepressant effect of SNSF and its central nervous system mechanism on depression-like behaviors, focusing on the prefrontal cortex (PFC) to dorsal raphe nucleus (DRN) neural circuit in a stress-induced adolescent animal model. Materials and methodsSNSF comprised four herbs, the root of Bupleurum chinense DC., the root of Paeonia lactiflora Pall., the fruit of Citrus aurantium L., the rhizome of Glycyrrhiza uralensis Fisch., in equal propotions. The adolescent depression animal model was induced by maternal separation (MS) and chronic restraint stress (CRS). In-vivo multichannel physiological electrodes were implanted into the PFC on PND 28 and animals were recorded 5 times during PND 35–46. From PND 47, the behavioral tests were performed to evaluate the antidepressant efficacy of SNSF. Subsequently, brain tissue was collected for Western blot and immunofluorescence staining analysis. Retro virus was injected into the DRN to explore sources of projections received by serotonergic (5-HTergic) neurons. And the PFC-to-DRN circuit was activated or inhibited through chemogenetic techniques to investigate the effects of SNSF on depression-like behaviors. ResultsAdministration of SNSF for 18 days effectively alleviated depression-like behaviors in MS&CRS adolescent mice. The PFC emerged as the primary glutamatergic projection source of the DRN5−HT neurons. Following SNSF administration for 13/15/18 days, there was an increase in the firing rate of excitatory neurons and excitatory/inhibitory (E/I) ratio in the PFC. MS&CRS stress let to a reduction in the density of 5-HT+ and CaMKII + neurons in the DRN, accompanied by an increase in the density of GAD + neurons in the DRN, while SNSF administration reversed the alterations. Chemogenetic activation of the PFC-to-DRN circuit rescued the depression-like behaviors induced by MS&CRS, whereas suppression of this circuit attenuated the antidepressant effect of SNSF. ConclusionsSNSF significantly mitigated depression-like behaviors in MS&CRS mice. SNSF exerts its antidepressant effects by increasing the E/I ratio in the PFC and enhancing glutamatergic projections from the PFC to the DRN.

Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota

Ethnopharmacological relevanceIn ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. Aim of the studyTo determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. Materials and methodsPotassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1β) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. ResultsIn this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1β. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. ConclusionRGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.

基于《伤寒论》治疗胸痹伴郁证的验案举隅

基于《伤寒论》治疗胸痹伴郁证的验案举隅

A Bibliophile in Shandong Province in the Republic of China Zhuang Enze and His Handwritten Copy of Shang Han Lun Xuan Zhu(Annotation of Treatise on Febrile Diseases)

Shang Han Lun Xuan Zhu(«»,Annotation of Treatise on Febrile Diseases) is a representative work of Zang Yingzhan, a famous physician in Zhucheng of Shandong who was as famous as Huang Yuanyu during the Qianlong period of the Qing Dynasty.The book was not published, but has been preserved only in manuscripts, of which 5 copies are now preserved.By comparing the five manuscripts seen, it is found that the Zhuang Enze version is unique in the existing version of this book, exquisite and generous, beautifully copied, with important documentary value. Zhuang Enze adopts the theories of various schools, supplements prescriptions, analyze medical theory with his unique insights.The reason may be related to his family's practice of medicine for generations, its philosophy of loving reading, copying books, and collecting books, and also related to its protection of local and state documents and the dissemination of lost culture.

Xiaoqinglong decoction improves allergic rhinitis by inhibiting NLRP3-mediated pyroptosis in BALB/C mice

Ethnopharmacological relevanceXiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. Aim of the studyNLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. Materials and methodsBALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. ResultsXQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1β and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. ConclusionsThe representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.

Elucidating the material basis and potential mechanisms of Daqinglong Decoction acting on influenza by UPLC-Q-TOF/MS and network pharmacology

Daqinglong Decoction (DQLD), a traditional Chinese medicine (TCM) prescription firstly recorded in Shang han lun (the treatise on febrile diseases), has been used hundreds of years for the clinical treatment of influenza. However, the chemical composition and therapeutic mechanism of this prescription are unclear. UPLC-Q-TOF/MS was employed to analyze the chemical compounds in both methanol and boiling water extracts of DQLD. The compounds were then screened, characterized, and filtered using the TCMSP, TCMIP, TCM-ID and SymMap database, with a focus on their oral bioavailability and drug-likeness values. The resulting data were analyzed and optimized using the R language platform, Autodock and Gromacs software to identify biological processes and pathways. A total of 121 compounds were identified, of which 5 showed good binding ability to influenza virus targets (1L1B, IL10, CASP3, STAT3, TNF, and others). The active ingredient-target-influenza virus pathway was constructed using a network drug target analysis model prediction of DQLD, which was mainly enriched in Human cytomegalovirus infection, PI3K-Akt, HIF-1, and other signaling pathways through 1L1B, IL10 and other targets. Those pathways highly correlated to the body’s inflammatory response, improve immunity, and exert anti-influenza virus effects. In summary, this study demonstrated that DQLD's active ingredients can effectively bind to influenza virus targets and exert anti-influenza virus effects by reducing inflammation and improving immunity through Human cytomegalovirus infection, PI3K-Akt and HIF-1 signaling pathways. These findings offer important insights into the potential mechanisms of action of DQLD and its potential use as a TCM against influenza and other viral infections. Communicated by Ramaswamy H. Sarma

The pharmacological mechanism of chaihu-jia-longgu-muli-tang for treating depression: integrated meta-analysis and network pharmacology analysis.

Aim: Chaihu-jia-Longgu-Muli-tang (CLM) is derived from "Shang Han Lun" and is traditionally prescribed for treating depression. However, there is still a lack of evidence for its antidepressant effects, and the underlying mechanism is also unclear. This study aimed to assess clinical evidence on the efficacy of CLM in patients with depression using a meta-analysis and to explore its underlying antidepressant molecular mechanisms via network pharmacology. Methods: Eight open databases were searched for randomized controlled trials (RCTs) comparing the effects of CLM alone or combined with serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) in patients with depression, evaluating the total effective rate of the treatment group (CLM alone or combined with SSRIs/SNRIs) and the control group (SNRIs or SSRIs), and comparing changes in depression scale, anxiety scale, sleep scale, inflammation indicators and adverse effects. Subsequently, the active ingredients and target genes of CLM were screened through six databases. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network and topology analysis were performed. Finally, Molecular docking was applied to evaluate the binding affinity between components and predicted targets. Results: Twenty-four RCTs with a total of 2,382 patients were included. For the efficacy of antidepression and adverse effects, whether CLM alone or in combination with SSRIs/SNRIs, the treatment group has no inferior to that of the control group. Additionally, the intervention of CLM + SSRI significantly improved the symptoms of anxiety and insomnia, and reduced serum IL-6 and TNF-α levels. For network pharmacology, a total of 129 compounds and 416 intersection targets in CLM were retrieved. The interaction pathway between CLM and depression is mainly enriched in PI3K-Akt, JAK-STAT, and NF-κB signaling pathway, PIK3R1, MAPK3, and AKT1 may be the potential targets of Stigmasterol, β-stiosterol, coumestrol. Conclusion: Compared to SSRIs/SNRIs alone, CLM is more effective and safe in treating depression. It not only significantly alleviates depressive mood, but improves symptoms such as anxiety and insomnia, with fewer side effects, especially in combination with SSRI. Its antidepressant mechanism may be correlated with the regulation of the PI3K/Akt signaling pathway and inhibiting inflammatory response.

What can traditional plant therapy do in the face of Covid-19? Examples from traditional Chinese medicine.

Until June 2022, more than 540.9 million people had been diagnosed with COVID-19, and the pandemic had claimed more than six million lives worldwide. Two years after fighting the virus, we faced a more uncertain position. SARS-CoV-2 is constantly mutating and reappears regularly, particularly with Omicron variants showing high genetic variation and immune escape mechanisms. The efficacy and duration of protection of existing vaccines against new variants of SARS-CoV-2 remains uncertain. The world needs time to develop new variant-specific drugs, including monoclonal topics, vaccines, and other antiviral drugs, to fight the epidemic. The aim of this study was to illustrate the scientific, effective and systematic nature of three classical prescriptions of traditional Chinese medicine (TCM) for the treatment of COVID-19 through comparison of disease symptoms, diagnostic process, and treatment methods and evidence-based and pharmacological studies. We analysed the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" (Version 9) made by China, "WHO-2019-nCoV-therapeutics", "Therapeutic Guidelines" published by Australian Therapeutic Guidelines Limited, "Shanghan Lun (Treatise on Febrile Diseases)", "Jinkui Yaolue (Golden Chamber Synopsis), and "Wenyi Lun (The Epidemic Febrile Disease)". We manually retrieved the dictionary of traditional Chinese medicine (Version II). In addition, we searched the Wiley online library, National Center for Biotechnology Information (NCBI), VIP, WHO website, and China National Knowledge Infrastructure (CNKI) for relevant literature from 2001 to 2022. We searched the original plants, ingredients, pharmacology, functions and indications, usage and dosage, drug efficacy, literature sources, and conduct an evidence-based studies. We quantified the strength of pharmacological action to show the pertinence of disease development. We found that the diagnosis and treatment of pulmonary infection caused by epidemic disease in TCM classics is consistent with the diagnostic process of modern medical therapeutic guidelines. The three classic prescriptions have significant symptomatic therapeutic effects on the respiratory, gastrointestinal, urinary and hematological symptoms of the clinical manifestations of COVID-19. It was found that the herbal functional group of Houpo (Cortex Magnoliae Officinalis), Chaihu (Radix Bupleuri), Cangzhu (Rhizoma Atractylodis), Qianghuo (Notopterygii Rhizoma et Radix), etc showed strong anti-inflammatory activity and had a positive effect on treating and preventing the outbreaks of systemic inflammatory factors. TCM can obtain obvious curative effect in symptomatic treatment, has strong anti-inflammatory effect, and can effectively reduce symptoms and patients' pain.

Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.

Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7cell model. The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.

Anti-arrhythmia potential of honey-processed licorice in zebrafish model: Antioxidant, histopathological and tissue distribution

Ethnopharmacological relevanceHoney-processed licorice (HPL) is the roasted product of licorice. It is recorded in the “Shang Han Lun” that licorice has better protection on heart after honey-processed. However, researches regarding its protective effect on the heart and the distribution of HPL in vivo are still limited. Aim of the studyTo evaluate the cardio-protection of HPL and explore the law of ten main components distribution in vivo under physiological and pathological conditions for an attempt to clarify the pharmacological substance basis of HPL in treating arrhythmia. Materials and methodsThe adult zebrafish arrhythmia model was established by doxorubicin (DOX). Electrocardiogram (ECG) was used to detect the heart rate changes of zebrafish. SOD and MDA assays were used to evaluate oxidative stress levels in the myocardium. HE staining was used to observe the morphological change of myocardial tissues after HPL treatment. The UPLC-MS/MS was adapted to detect the content of ten main components of HPL in heart, liver, intestine, and brain under normal and heart injury conditions. ResultsHeart rate of zebrafish was decreased, the SOD activity was attenuated and MDA content was increased in myocardium after administration of DOX. Moreover, tissue vacuolation and inflammatory infiltration were detected in zebrafish myocardium induced by DOX. HPL could ameliorate heart injury and bradycardia induced by DOX to a certain extent by increasing SOD activity and reducing MDA content. In addition, the study of tissue distribution revealed that the content of liquiritin, isoliquiritin, and isoliquiritigenin in the heart was higher in the presence of arrhythmias than those in the normal condition. Under pathological conditions, the heart highly exposed to these three components could elicit anti-arrhythmic effects by regulating immunity and oxidation. ConclusionThese findings indicate that the HPL is protective against heart injury induced by DOX, and its effect is associated with the alleviation of oxidative stress and tissue injury. And the cardioprotective effect of HPL under pathological conditions may be related to the high distribution of liquiritin, isoliquiritin, and isoliquiritigenin in heart tissue. This study provides an experimental basis for the cardioprotective effects and tissue distribution of HPL.

Wu Shou and his work Shang Han Yun Yao Quan Shu published in the Ming Dynasty

Wu Shou was a doctor in a medical family in Qiantang, Zhejiang in the Ming Dynasty. He was promoted as a medical officer in the local government and the Imperial Academy of Medicine. His work, considered a masterpiece Shang Han Yun Yao Quan Shu was published around 1505. The series consisted of four volumes. The main content of the book focused on the taxonomy study to the Treatise on Febrile Diseases (Shang Han Lun). Wu Shou was politically accused of being a person who pursued fame and fortune but lacked medical skills because of the conflicts and contradiction between medical officials and the political service system in the period of the Chenghua and Hongzhi in the Ming Dynasty. However, his medical and academic thinking and skills for typhoid treatment shown in the book demonstrated that they were not as awful as what was described at that time.

The inscription of Treatise on Febrile Diseases by Zhao Kaimei and the position of its attached official dispatch and name by the Imperial College of the Northern Song Dynasty

The Treatise on Febrile Diseases (Shang Han Lun) inscripted and published by Zhao Kaimei in the Ming Dynasty was believed to be reprinted from the version of the Northern Song Dynasty, based on its official dispatch, at the beginning of the book, in the third year of the Yuanyou Period of the Northern Song Dynasty. However, the authenticity of the official dispatch remained controversial among scholars of medical history and literature. This paper reports on an investigation of the formation process of the official dispatch, classifies the titles recorded after the inscription, makes comparisons with the medical books inscripted in the same period, and analyzes the causes of the official dispatch and the title in Treatise on Febrile Diseases inscripted by Zhao Kaimei. It was found that the inscription, the official dispatch and the titles were authentic and that the position of the official dispatch was moved from the end of the book to the beginning of the book.

Connotation of Xiao Chaihu Decoction combined with Maxing Shigan Decoction based on severe cases and modern pathophysiological mechanism and application for severe pulmonary infection and acute exacerbation of chronic obstructive pulmonary disease in critical care medicine

Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic herbal formula. All of them are derived from Treatise on Cold Damage(Shang Han Lun) by ZHANG Zhong-jing. This combination has the effects of harmonizing lesser yang, relieving exterior syndrome, clearing lung heat, and relieving panting. It is mainly used for treating the disease involving the triple-Yang combination of diseases and accumulation of pathogenic heat in the lung. Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic combination for the treatment of exogenous diseases involving the triple-Yang combination. They are commonly used in exogenous diseases, especially in the north of China. This combination is also the main treatment strategy for coronavirus disease 2019(COVID-19) accompanied by fever and cough. Maxing Shigan Decoction is a classical herbal formula for treating the syndrome of phlegm-heat obstructing the lung. "Dyspnea after sweating" suggests the accumulation of pathogenic heat in the lung. Patients with mild symptoms may develop cough and asthma along with forehead sweating, and those in critical severe may develop whole-body sweating, especially the front chest. Modern medicine believes that the above situation is related to lung infection. "Mild fever" refers to syndromes rather than pathogenesis. It does not mean that the heat syndrome is not heavy, instead, it suggests that severe heat and inflammation have occurred. The indications of Xiao Chaihu Decoction combined with Maxing Shigan Decoction are as follows.(1) In terms of diseases, it is suitable for the treatment of viral pneumonia, bronchopneumonia, lobar pneumonia, mycoplasma pneumonia, COVID-19 infection, measles with pneumonia, severe acute respiratory syndrome(SARS), avian influenza, H1N1 influenza, chronic obstructive pulmonary disease with acute exacerbation, pertussis, and other influenza and pneumonia.(2) In terms of syndromes, it can be used for the syndromes of bitter mouth, dry pharynx, vertigo, loss of appetite, vexation, vomiting, and fullness and discomfort in the chest and hypochondrium. It can also be used to treat alternate attacks of chill and fever and different degrees of fever, as well as chest tightness, cough, asthma, expectoration, dry mouth, wanting cold drinks, feeling agitated, sweating, yellow urine, dry stool, red tongue, yellow or white fur, and floating, smooth, and powerful pulse, especially the right wrist pulse.

The sources and spread of Zhong Jing Quan Shu related to Zhang Qingzi

The original version and title of Zhong Jing Quan Shu referred to the collection of four books - Shang Han Lun, Zhu Jie Shang Han Lun, Shang Han Lei Zheng and Jin Gui Yao Lue Fang Lun, published by Zhao Kaimei in the Ming Dynasty. Then, Zhang Qingzi Shang Han Lun was written by Zhang Qingzi. After that, a Japanese scholar compiled a new collection based on Zhong Jing Quan Shu held in the Cabinet Library in Japan consisting of three books - Shang Han Lei Zheng, JinGui Yao Lue Fang Lun and Zhang Qingzi Shang Han Lun. The preface and content in this collection was adjusted for some practical purposes and was published in the second year of Manji in Japan (1659). This book, Zhang Qingzi Shang Han Lun was based on Shang Han Lun from the early and mid-Edo period of Japan. It was then returned to China in the Guangxu period of the Qing Dynasty. It was soon republished by Deng in Chengdu, with Yun Qi Zhang Jue Lu and Shang Han Ming Li Lun, added as a collection of five books with the same name Zhang Zi Qing Shang Han Lun, being popular in the late Qing Dynasty and the Republic of China. This book was understood to be from Zhong Jing Quan Shu published by Zhao Kaimei during this period. These two books were distinguished from each other when Shang Han Lun published in the Song Dynasty, drew people's attention. However, Zhang Qingzi Shang Han Lun was still believed valuable for both clinical and literature studies.

Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of γδT17 cells

BackgroundCurrent therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified. PurposeWe aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms. MethodsThe protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate. ResultsMGQD alleviated DSS‑induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome. ConclusionThe mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

On the Embodiment of "to Moisten the Dryness" in the Treatment of Typhoid Fever

Su Wen Zhi Zhen Yao Da Lun says: "Dryness need to be nurtured", meaning that using moistening prescriptions treats "the dreness". "The dreness" can be divided into Intrinsic dreness which caused by the shortages of body fluid and foreign dreness which caused by pathogenic factors. "The dreness" in Shang Han Lun mainly means that intrinsic dreness wastes body fluid, influencing progress and prognosis of disease. besides the dreness, there are phenomenon of disharmony between ying and wei, intense heat of Yang Ming, Depression heat of lung, dreness and blocking, Gastric fever restricting the spleen, the disfunction of "Shu Ji", so Zhang Zhongjing establishs therapys of regulating Ying and Wei, Pungent and cold to clear heat, using cold and hot medicine meanwhile, expelling by attacking, expelling by moistening, mediating "Shao Yang", reflecting that Zhang zhongjing treats disease from the root.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Effects of n-butanol extract of Pulsatilla decoction on the NLRP3 inflammasome in macrophages infected with Candida albicans

Ethnopharmacological relevancePulsatilla decoction is a traditional Chinese medicine from Shang Han Lun that has been reported to have therapeutic efficacy in vulvovaginal candidiasis (VVC), and is a growth inhibitor of Candida albicans (C. albicans) in vitro, the causative agent of VVC.Aim of the study: In previous studies, Pulsatilla decoction has shown therapeutic benefits for VVC. With further chemical extraction of the decoction, the n-butanol extract (of Pulsatilla decoction; BEPD) was most effective against C. albicans and therapeutic for VVC. The mechanism, however, has not been elucidated. The regulation of NOD-like receptor protein 3 (NLRP3) inflammasome has recently been demonstrated as a critical component of the inflammasome complex that initiates the vaginal inflammatory response. Therefore, the effect of BEPD on NLRP3 associated with VVC was investigated. Materials and methodsUltra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for detecting the principal compounds of BEPD (Anemoside B4, Esculin, esculetin, Epiberberine, Berberine, Jatrorrhizine and Phellodendrine). BEPD-containing serum is prepared by intragastric administration of BEPD (4.6875 g/kg for seven days) in rats. PMA-induced THP-1 cells were challenged with C. albicans. The expression of CD68 to identify macrophages was examined by flow cytometry, the viability of THP-1 cells were assessed by CCK8 assay, the release of lactate dehydrogenase (LDH) was detected by LDH kit, and the secretion levels of IL-1β and IL-18 were evaluated through enzyme-linked immunosorbent assay (ELISA), the levels of NLRP3 were quantified by immunofluorescence, the levels of reactive oxygen species (ROS) were measured by ROS kit, and the expression of Dectin-1, Syk, TLR2, TLR4, MyD88, NF-κB, NLRP3, Caspase-1, and ASC proteins were detected by Western blot. ResultsAfter administration of BEPD-containing serum, the levels of IL-1β, IL-18 and LDH released from macrophages were reduced in the BEPD-containing serum group compared to the model group. In addition, BEPD-containing serum inhibited the expression of ROS in macrophages, suppressed the expression of NLRP3 and inhibited the expression of TLRs/MyD88 and Dectin-1/Syk signaling pathway-related proteins. ConclusionsBEPD suppressed the NLRP3 inflammasome and related signaling pathways in macrophages infected with C. albicans in vitro, thereby providing insight into the mechanism of BEPD action on VVC.

Heterogeneous graph construction and node representation learning method of Treatise on Febrile Diseases based on graph convolutional network

ObjectiveTo construct symptom-formula-herb heterogeneous graphs structured Treatise on Febrile Diseases (Shang Han Lun,《伤寒论》) dataset and explore an optimal learning method represented with node attributes based on graph convolutional network (GCN). MethodsClauses that contain symptoms, formulas, and herbs were abstracted from Treatise on Febrile Diseases to construct symptom-formula-herb heterogeneous graphs, which were used to propose a node representation learning method based on GCN − the Traditional Chinese Medicine Graph Convolution Network (TCM-GCN). The symptom-formula, symptom-herb, and formula-herb heterogeneous graphs were processed with the TCM-GCN to realize high-order propagating message passing and neighbor aggregation to obtain new node representation attributes, and thus acquiring the nodes’ sum-aggregations of symptoms, formulas, and herbs to lay a foundation for the downstream tasks of the prediction models. ResultsComparisons among the node representations with multi-hot encoding, non-fusion encoding, and fusion encoding showed that the Precision@10, Recall@10, and F1-score@10 of the fusion encoding were 9.77%, 6.65%, and 8.30%, respectively, higher than those of the non-fusion encoding in the prediction studies of the model. ConclusionNode representations by fusion encoding achieved comparatively ideal results, indicating the TCM-GCN is effective in realizing node-level representations of heterogeneous graph structured Treatise on Febrile Diseases dataset and is able to elevate the performance of the downstream tasks of the diagnosis model.

Construction and application of knowledge graph of Treatise on Febrile Diseases

ObjectiveTo establish the knowledge graph of “disease-syndrome-symptom-method-formula” in Treatise on Febrile Diseases (Shang Han Lun,《伤寒论》) for reducing the fuzziness and uncertainty of data, and for laying a foundation for later knowledge reasoning and its application. MethodsUnder the guidance of experts in the classical formula of traditional Chinese medicine (TCM), the method of “top-down as the main, bottom-up as the auxiliary” was adopted to carry out knowledge extraction, knowledge fusion, and knowledge storage from the five aspects of the disease, syndrome, symptom, method, and formula for the original text of Treatise on Febrile Diseases, and so the knowledge graph of Treatise on Febrile Diseases was constructed. On this basis, the knowledge structure query and the knowledge relevance query were realized in a visual manner. ResultsThe knowledge graph of “disease-syndrome-symptom-method-formula” in the Treatise on Febrile Diseases was constructed, containing 6 469 entities and 10 911 relational triples, on which the query of entities and their relationships can be carried out and the query result can be visualized. ConclusionThe knowledge graph of Treatise on Febrile Diseases systematically realizes its digitization of the knowledge system, and improves the completeness and accuracy of the knowledge representation, and the connection between “disease-syndrome-symptom-treatment-formula”, which is conducive to the sharing and reuse of knowledge can be obtained in a clear and efficient way.