Shang Han Lun Research Articles

The understanding of epidemic diseases in the Qin and Han Dynasties

In the Qin and Han Dynasties, three views were argued as the main causes of epidemic diseases, the observation of climate, the interaction between nature and humans and 'witchcraft'. Specifically it was thought that abnormal climate, personnel and government decree, and 'gods' and 'ghosts' were responsible for epidemics. This perception led to corresponding countermeasures to deal with epidemic diseases. The abnormal climate in nature was believed to result in the occurrence of epidemic diseases. This was interpreted by traditional Chinese medicine in terms of exogenous diseases. For instance, Huang Di Nei Jing interpreted leprosy with the point of wind-pathogen attacking. Shang Han Lun treated epidemic diseases with the viewpoint of exogenous pathogen. The classic books of Chinese materia medica recorded many cases of preventing and treating epidemic diseases with materia medica. The personnel and government decree refers to the wrong decrees of Emperors and the poor implementation of officials. This was argued to lead to various disasters including epidemic diseases. It was interpreted by Dong Zhongshu, a famous Confucian in the Han Dynasty, as the punishment of gods upon their misconduct. This reminded emperors about reflecting on the epidemic diseases and correcting their mistakes politically. 'Gods' and 'ghosts' were also believed as the cause of epidemics. This idea drove people to deal with epidemic diseases through sacrifices and exorcism.

Influence of Huangqin Decoction on the immune function and fecal microbiome of chicks after experimental infection with Escherichia coli O78

Huangqin Decoction (HQD), a traditional Chinese medicine formula from the Shang Han Lun written by Zhang Zhongjing, has been used in China for nearly two thousand years. According to the traditional Chinese medicine and previous literature, HQD has the effect of clearing heat, removing toxins, relieving diarrhea and pain. Therefore, HQD was used to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. The effect of HQD, one-herb-absent HQD treatments and enrofloxacin (ENR) on the average daily gain (ADG), mortality rates, visceral index and toll-like receptors (TLRs), inflammatory factors and intestinal microflora in E. coli O78-inoculated chicks were investigated. HQD supplementation increased ADG and reduced the mortality rates caused by E. coli challenge, decreased the heart, liver, bursa of Fabricius (BF) and spleen index. HQD supplementation decreased the serum lysozyme (LZM), IL-1β, TNF-α, IL-10, IL-6 level, down-regulated the mRNA expression of TLR4, -5 and -15 in the spleen by E. coli challenged chicks, and up-regulated the mRNA expression of TLR4, -5 and -15 in BF. At the phylum level, HQD supplementation reversed the increase of Operational Taxonomic Unit (OTUs), decreased the relative abundance of harmful bacteria Proteobacteria, increased the relative abundance of probiotic bacteria Bacteroidetes and Firmicutes. At the genus level, HQD decreased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas. It means that HQD treatment reversed the change of the gut microbiota structure. Compared with HQD, HQD-DZ and HQD-HQ increased the mortality rates. HQD-HQ decreased the ADG and liver index. HQD-GC decreased the spleen index. All herb-absent increased the serum IL-6, but only the HQD-HQ and HQD-SY increased the serum TNF-α. All herb-absent did not activate the TLRs signaling pathways in spleen and BF of chicks. The harmful bacteria Escherichia-Shigella were increased in HQD-HQ and HQD-DZ treatments. HQD-DZ treatment also increased the level of Proteobacteria. The results showed that dietary supplementation with HQD, by down-regulating the mRNA expression of TLR4, -5 and -15 in the spleen, further decreasing the serum LZM and IL-1β, TNF-α, IL-10, IL-6 level, improves the immune function and reverses the change of fecal microbiome in chicks challenged with E. coli. In herb-absent supplementation, the results showed that SY and DZ play a key role in reducing the levels of inflammatory factors and keeping fecal microbiome balance respectively. More importantly, HQ is indispensable in HQD, not only play a key role in reducing the level of inflammatory factors, but also in keeping the balance of fecal microflora.

XCHT alleviates the pancreatic fibrosis via VDR/NLRP3 signaling pathway in a mouse model of CP

Ethnopharmacological relevanceXiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. Aim of the studyThis study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. Materials and methodsFifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 μg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. ResultsThe pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1β, TNF-α and IL-6. ConclusionsThese results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.

Gegen Qinlian decoction ameliorates murine colitis by inhibiting the expansion of Enterobacteriaceae through activating PPAR-γ signaling

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae, maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli (E. coli, family of Enterobacteriaceae) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae. Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier

BackgroundThe clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PurposeThe present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. MethodsThe therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. ResultsHQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. ConclusionsThese findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.

Influence of Gegenqinlian Decoction on Pharmacokinetics and Pharmacodynamics of Atorvastatin Calcium in Hyperlipidemic Rats.

Gegenqinlian decoction (GQD), a classic traditional Chinese medicine (TCM), was described in Shanghan Lun. GQD is often combined with antihyperlipidemic drugs (mainly atrovastatin calcium) in TCM clinics. However, the herb-drug interaction between GQD and atrovastatin calcium (AC) is still unknown. To determine whether the combination is safe, we evaluated the effects of GQD on the activities of cytochrome P450 (CYP)3A2 enzyme and investigated the impact of GQD on the pharmacokinetics and pharmacodynamics of AC in rats. The pharmacokinetics of AC (10mg/kg) with or without pretreatment with GQD (freeze-dried powder, 1.35g/kg) were investigated using HPLC. The influence of GQD on pharmacodynamics of AC were determined by detecting the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, the probe drug method was used to explore the effect of GQD on CYP3A2 activity. The pharmacokinetic parameters of AC combined with GQD were significantly affected (P<0.05) in hyperlipidemic rats. The serum TC, TG and LDL-C levels of the combination were significantly reduced (P<0.05), and the serum HDL-C level was significantly increased (P<0.05) compared with AC/GQD alone. AST and ALT activities treated with both GQD and AC+GQD group were significantly reduced (P<0.05) compared with AC group. There was a significant difference in the pharmacokinetic parameters of midazolam between control and GQD groups (P<0.05). Maximum concentration (Cmax), area under the concentration-time curve(AUC) from time 0 to the last quantifiable concentration(AUC0-t)and AUC from time 0 to infinity (AUC0-∞) increased significantly in GQD group. The result suggested that GQD combined with AC can improve the lipid-lowering effect of AC and reduce the damage of AC to the liver simultaneously. However, GQD can inhibit the activity of CYP3A2 in hyperlipidemic rats and increase the blood concentration of AC. Therefore, the clinical dose of AC should be adjusted when they are combined. Sincethe study was conducted in rats, further research should be carried out to assess the uniformity of the pharmacokinetics and pharmacodynamics between rats and humans.

Coptis chinensis and dried ginger herb combination inhibits gastric tumor growth by interfering with glucose metabolism via LDHA and SLC2A1

Ethnopharmacological relevanceCoptis chinensis Franch (CC) and Zingiber officinale Roscoe (dried ginger; DG) are traditional Chinese medicines. CC can dry dampness, relieve fire and detoxify, and is used to treat gastritis, gastric ulcer, colitis. DG can warm spleen and stomach for dispelling cold, used for the treatment of spleen and stomach deficiency. Both CC and DG are widely used to treat gastrointestinal diseases. CC-DG herb medicine combination originates from Huanglian decoction and Pinellia xiexin decoction in “Shanghan Lun” to comfort the stomach and intestines. CC and DG are used for the treatment of nausea and choking diaphragm which highly associated with gastric cancer clinically in ancient time. Aim of the studyThis study aimed to investigate the effects and underlying molecular mechanisms of CC-DG combination on gastric cancer. Materials and methodsThe CC-DG extract was subjected to HPLC analysis. Viability (MTT) and cytotoxicity (CCK8) assays were performed using the SGC7901 and MFC cells. Cell cycle and apoptosis were measured by flow cytometry. The mRNA expression levels were measured by RT-PCR. In vivo anti-tumor activity of CC-DG was assessed in a tumor xenograft model. ResultsTwelve different proportions of CC-DG were tested for inhibitory effects on gastric cancer cells; CC-DG ratio 1:1 was found most effective. CC-DG administration significantly reduced the cell proliferation, migration, and colony formation, while increased cell apoptosis compared with the control group. CC-DG regulated differentially expressed genes in SGC7901 cells were subjected to pathway enrichment analysis. CC-DG significantly inhibited the cell glucose metabolism, downregulated the expression of LDHA and SLC2A1 genes, and changed the expression of other related genes including ME2, LDHD, LDHB, HIF1A, PKM, Pcx, and Got1. In addition, CC-DG suppressed tumorigenesis and inhibited MKI67 expression in the tumor xenograft model. ConclusionsCC-DG inhibited the proliferation, migration, invasion of SGC7901/MFC gastric cells, and in turn, suppressed tumorigenesis by regulating glucose metabolism through regulation of LDHA and SLC2A1 genes.

Network Analysis on Herbal Formulas from Wenrejingwei and Shang Han Lun.

ObjectivesThis study aims to describe the utilization of herbal formulas from Wenrejingwei by using network analysis and understand the treatment of acute exogenous febrile diseases.MethodsWe constructed a matrix of high-frequency herbal combinations (HCs) from Wenrejingwei and Shang Han Lun and cluster networks based on cohesive analysis. Network analysis was performed to compare the results.ResultsThe results of the high-frequency HC network in Wenrejingwei showed cohesive patterns in three categories corresponding to dampness-heat and warm-fever treatment. Compared to the Shang Han Lun network, the Wenrejingwei network indicated a careful approach in the use of pungent and warm herbs such as Guizhitang. Moreover, the combination of Scutellaria baicalensis and Coptis chinensis along with the use of herbs strengthening yin, such as Ginseng Radix and Liriopes Radix, provide evidence of a holistic approach in the treatment of exogenous febrile diseases by considering the balance of the human body damaged by heat.ConclusionThe results of this study could help select appropriate herbal formulas and treatment methods for treating Onbyeong and modern acute febrile infectious diseases.

Study on the experimental verification and regulatory mechanism of Rougui-Ganjiang herb-pair for the actions of thermogenesis in brown adipose tissue based on network pharmacology

Ethnopharmacological relevanceCinnamomum cassia Presl (Rougui) has character of xin、gan、wen, belongs to Jing of heart、lung、bladder, and has the effect of dispersing cold and relieving pain. It is widely used to resolve the exterior and dissipate cold in Treatise on Febrile Diseases (Shang Han Lun), such as Chaihu Guizhi Ganjiang Tang and Guizhi Renshen Tang. Both these two prescriptions contain Cinnamomum cassia Presl and Zingiber officinale Rosc (Ganjiang). Rougui-Ganjiang herb-pair (RGHP) can warm viscera and remove cold, which is widely used in Shang Han Lun. And in modern times, recent studies have showed that cinnamon and ginger also have the effect of thermogenesis and regulating the body temperature, respectively. Aim of the studyTo maintain the body thermal homeostasis and prevent cold invasion of main organs, in this study, we assessed the underlying physiological changes induced by RGHP in mice exposed to −20 °C and explored the mechanisms for the thermogenic actions of RGHP in brown adipose tissue (BAT) by network pharmacology and molecular docking. Materials and methodsMale Kunming (KM) mice were fed normal diet with orally administration of distilled water or ethanol RGHP extract (three doses: 375,750 and 1500 mg/kg) for 21 days, once per day and then exposed to −20 °C for 2 h. The core temperature, activity ability and the degree of frostbite in mice, morphological and ATP content of adipocytes were measured. In addition, the network pharmacology was employed to predict the targets of RGHP’ s thermogenesis effect on BAT. Pathway analysis and biological process with key genes was carried out through KEGG and GO analysis, respectively. Furthermore, the core ingredients and targets obtained by network pharmacology were verified by molecular docking and Western blot assays. ResultsRGHP can significantly increase the core body temperature, reduce the degree of frostbite and enhance the activity ability of mice after cold exposure. Meanwhile, it can also improve the lipid morphology and decrease ATP production in BAT. A network pharmacology-based analysis identified 246 ingredients from RGHP (two herbs), which related to 222 target genes. There were 8 common genes between 222 compounds target genes and 62 thermogenesis associated target genes, which linked to 49 potential compounds. There are 24 ingredients which degree are greater than the average. Among them, we found that oleic acid, EIC, 6-gingerol, eugenol, isohomogenol and sitogluside could be detected in mice plasma. The cAMP-PPAR signaling pathway was enriched for thermogenesis after KEGG analysis with 8 genes. Molecular docking analysis and Western blot assay further confirmed that oleic acid, 6-gingerol, eugenol and isohomogenol were potential active ingredients for RGHP's heat production effect. And UCP1, PGC-1α, PPARα and PPARγ are key thermogenesis proteins. ConclusionsRGHP treatment can significantly maintain the rectal temperature of mice by enhancing the BAT heat production. RGHP exhibited the heat production effect, which might be mainly attributed to increasing thermogenesis through the cAMP-PPAR signaling pathway in cold exposure mice. Oleic acid, 6-gingerol, eugenol and isohomogenol might be considered the potential therapeutic ingredients which affect the key targets of thermogenesis effect.

Exploration of the potential mechanism of Banxia Xiexin Decoction for the effects on TNBS-induced ulcerative colitis rats with the assistance of network pharmacology analysis

Ethnopharmacological relevanceBanxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant. Aim of the studyThis study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research. MethodsFifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1β, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the “herbs-components-targets-disease” network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out. ResultsThe results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.

Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway.

Background: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hypothesis was proposed that the multi-target solution of GGQLD produced anti-inflammatory effects on ameliorating hyperuricemia (HUA). Methods: A total of 30 primary HUA patients receiving GGQLD treatment (two doses daily) for 4 weeks were selected. Then, differences in uric acid (UA) levels and expression of peripheral blood mononuclear cells (PBMCs) and urinary exosomes before and after treatment were analyzed. The therapeutic indexes for the active ingredients in GGQLD against HUA were confirmed through pharmacological subnetwork analysis. Besides, the HUA rat model was established through oral gavage of potassium oxonate and treated with oral GGQLD. In addition, proximal tubular epithelial cells (PTECs) were stimulated by UA and intervened with GGQLD for 48 h. Subsequently, RNA-seq, flow cytometry, and confocal immunofluorescence microscopy were further conducted to characterize the differences in UA-mediated inflammation and apoptosis of human renal tubular epithelial cells pre- and post-administration of GGQLD. In the meanwhile, quantitative real-time PCR (qPCR) was carried out to determine gene expression, whereas a western blotting (WB) assay was conducted to measure protein expression. Results: Our network analysis revealed that GGQLD treated HUA via the anti-inflammatory and antiapoptotic pathways. Additionally, NLPR3 expression significantly decreased in PBMCs and urinary exosomes of HUA patients after GGQLD treatment. In vivo, GGQLD treatment alleviated HUA-induced renal inflammation, which was associated with decreased expression of NLRP3 inflammasomes and apoptosis-related mRNAs. Moreover, GGQLD promoted renal UA excretion by inhibiting the activation of GSDMD-dependent pyroptosis induced by NLRP3 inflammasomes and by reducing apoptosis via the mitochondrial apoptosis signaling pathway in vitro. Conclusion: This study indicates that GGQLD efficiently reduces inflammatory responses while promoting UA excretion in HUA. Our findings also provide compelling evidence supporting the idea that GGQLD protects against the UA-mediated renal tubular epithelial cell inflammation through the mitochondrial apoptosis signaling pathways. Taken together, these findings have demonstrated a novel therapeutic method for the treatment of HUA.

Application of Chinese Herbal Medicine in COVID-19

Traditional Chinese herbal medicine has a long history in treating febrile diseases, according to the Shang Han Lun, a classical theory of traditional Chinese medicine developed by Zhang Zhongjing in the Han Dynasty. Some herbs have been formulated as prescription formulae or manufactured as finished medicine such as pills, capsules or injections. The Chinese government has recommended specific TCM prescriptions alone or combined with Western medicine to treat patients with COVID-9. Here, we introduce three prescription formulae, Qingfei Paidu Decoction, Huashi Baidu Formula, and Xuanfei Baidu Formula, three finished medicines, Lianhua Qingwen Capsule, Jinhua Qinggan Granule, and Xuebijing Injection; following this, several single herbs such as Ephedra herba, Honeysuckle, Scutellaria, Glycyrrhizae radix, Armeniacae semen, Sophorae flavescentis radix, and Curcuma longa. We review existing evidence of these traditional medicines and herbs for their related antiviral activities, efficacy, and underlying mode of action in virus-related diseases. Most of these drugs have been traditionally used in Chinese medicine for over a thousand years, and they have been proved to be safe in treating flu-like virus infections. It will be adequate to further test for their efficacy for COVID-19 and understand the underlying molecular mechanism.

Effects of Huangqin Decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology

Ethnopharmacological relevanceHuangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. ObjectiveTo investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). MethodsThe bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H–C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. ResultsThe results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H–C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. ConclusionsHQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.

Interview with Dr. Liu Qingquan: Traditional Chinese Medicine for COVID-19 Diagnosis and Treatment

Interview with Dr. Liu Qingquan: Traditional Chinese Medicine for COVID-19 Diagnosis and Treatment

Tongmai Yangxin pill reduces myocardial No-reflow via endothelium-dependent NO-cGMP signaling by activation of the cAMP/PKA pathway

Ethnopharmacological relevanceThe Tongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease. Previous studies have confirmed that TMYX can improve vascular endothelial function in patients with coronary heart disease by upregulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels remains unclear. Aim of the studyThis study aimed to reveal whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels. The underlying cAMP/PKA and NO-cGMP signaling pathway-dependent mechanism is also explored. Materials and methodsThe left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish the NR model. TMYX (4.0 g/kg) was orally administered throughout the experiment. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were used to evaluate the NR and ischemic areas. Pathological changes in the myocardium were assessed by hematoxylin–eosin staining. An automated biochemical analyzer and kit were used to detect the activities of myocardial enzymes and myocardial oxidants, including CK, CK-MB, LDH, reactive oxygen species, superoxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins related to the cAMP/PKA and NO/cGMP signaling pathways were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was used to detect coronary artery diastolic function in vitro. ResultsTMYX elevated the EF, FS, LVOT peak, LVPWd and LVPWs values, decreased the LVIDd, LVIDs, LV-mass, IVSd, and LV Vols values, demonstrating cardio-protective effects, and reduced the NR and ischemic areas. Pathological staining showed that TMYX could significantly reduce inflammatory cell number and interstitial edema. The activities of CK, LDH, and MDA were reduced, NO activity was increased, and oxidative stress was suppressed after treatment with TMYX. TMYX not only enhanced the expression of Gs-α, AC, PKA, and eNOS but also increased the expression of sGC and PKG. Furthermore, TMYX treatment significantly decreased ROCK expression. We further showed that TMYX (25–200 mg/mL) relaxed isolated coronary microvessels. ConclusionsTMYX attenuates myocardial NR after ischemia and reperfusion by activating the cAMP/PKA and NO/cGMP signaling pathways, further upregulating NO activity and relaxing coronary microvessels.

Narrative review of the mechanisms of action of dachengqi decoction in the treatment of hyperlipidemic pancreatitis on six-hollow-organs to be unblocked theory

The incidence rate of acute pancreatitis (AP) caused by hyperlipidemia is increasing year by year. The primary treatment goal is to reduce blood lipids rapidly. On the theory of "Six-hollow-organs to be unblocked" we used dachengqi decoction (original prescription of Zhang Zhongjing in Shanghan Lun) to block the peroxisome proliferator-activated receptor γ (PPARG) pathway and rapidly reduce blood lipid to achieve the purpose of treating hyperlipidemic acute pancreatitis (HLAP). In this review, we summarize the etiology and pathogenesis of HLAP and the progress of traditional Chinese medicine in treating HLAP. The mechanisms of action of dachengqi decoction in the treatment of HLAP and the involvement of the PPARG pathway were discussed. In brief, the dachengqi decoction has the effect of resolving phlegm and clearing waste substances and can improve intestinal function; can inhibits the production of interleukin-1, interleukin-6, and tumor necrosis factor-α, and reduces the damage of SIRS to human body; also it improves the microcirculation system by inhibiting the production of inflammatory factors, reducing, or eliminating the damage to vascular endothelial cells and microvessels, and improving vascular permeability. The clarification of the mechanisms of action of the drug is conducive to the extensive clinical application of the classical formula.

Tongmai Yangxin pill reduces myocardial no-reflow by regulating apoptosis and activating PI3K/Akt/eNOS pathway

Ethnopharmacological relevanceTongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty and was further improved by Professor Ruan Shiyi, a cardiovascular expert at Tianjin University of Traditional Chinese Medicine. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease and can improve vascular endothelial function in patients with angina pectoris or coronary heart disease by up-regulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial no-reflow by up-regulating NO activity and then dilating blood vessels remains unclear. Aim of the studyThis study aimed to reveal whether TMYX can further improve myocardial NR by up-regulating NO activity and then dilating blood vessels. The mechanism underlying PI3K/Akt/eNOS pathway activation and apoptosis regulation is also explored. Materials and methodsThe left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish a NR model. The rats were assigned to 14 groups: control, sham, NR, TMYX (4.0 g/kg), sodium nitroprusside (SNP), Tongxinluo capsule (TXL), PI3K blocker (LY), TMYX + LY, SNP + LY, TXL + LY, eNOS blocker (L-NAME), TMYX + L-NAME, SNP + L-NAME, and TXL + L-NAME groups. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were adopted to evaluate NR and ischemic areas. Cell inflammation degree and edema were assessed by hematoxylin–eosin staining. Automated biochemical analyzer and kit were used to detect the activities of myocardial oxidants, including reactive oxygen species, super oxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins in the PI3K/Akt/eNOS signaling pathway and apoptosis were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was adopted to detect coronary artery diastolic function in vitro. ResultsTMYX reduced NR and ischemic areas; suppressed LV-mass; enhanced EF, FS, LVOT peak, and LVSV; and improved cardiac structure and function. Moreover, it decreased creatine kinase (CK), CK-MB, and lactic dehydrogenase activities. TMYX increased NO and super oxide dismutase activities; inhibited malonaldehyde activity; reduced muscle fiber swelling and inflammatory cell infiltration; and improved vasodilation in vitro. In the NR myocardium, TMYX stimulated myocardial PI3K activities and PI3K (Tyr458) phosphorylation and enhanced Akt activities and Akt phosphorylation at Tyr315. TMYX increased the activities of eNOS and the phosphorylation of eNOS at Ser1177 in the NR myocardium and attenuated cardiomyocyte apoptosis by increasing the expression of Bcl-2 and decreasing that of caspase-3 and Bax. All these effects of TMYX were abolished by the specific inhibitors of PI3K (LY) and eNOS (L-NAME). ConclusionsTMYX attenuates myocardial NR after ischemia and reperfusion by activating the PI3K/Akt/eNOS pathway and regulating apoptosis, further up-regulating NO activity and relaxing coronary microvessels.

Epidemic Diseases and Chinese Medicine: Example of Severe Acute Respiratory Syndrome and COVID-19.

Epidemic diseases, known and studied in China since antiquity, are one of the main chapters of the School of Exogenous Febrile Diseases (). Along with the legends about epidemic demons, China has developed over the centuries a medical approach based on the teachings of Huang Di Nei Jing (Internal Classic), Nan Jing (Classic of Difficulties), and Shang Han Lun (Treatise of Harmful Cold). However, it was in the 17th century, after the great break of the Song, Jin, and Yuan eras that an innovative spirit Wu Youxing () first foresaw the existence of microorganisms as we know them now. His Wen Yi Lun (Treatise on Pestilences) foreshadows an original approach to epidemic diseases, particularly emerging infectious diseases of the 21st century: severe acute respiratory syndrome 2003-2004 and the COVID-19 pandemic are perfect examples. In this first article, which will be followed by two others, we will examine the classical and modern Chinese definitions of these dreadful plagues.

Protective effects of Lizhong decoction on ulcerative colitis in mice by suppressing inflammation and ameliorating gut barrier

Ethnopharmacological relevanceLizhong Decoction (LZD) is a classical prescription firstly recorded in “Shanghan Lun”. It has been used to clinically treat ulcerative colitis (UC) for thousands of years. However, its mechanism is not clear up to now. Aim of the studyThe goal of this study was to assess the amelioration of LZD on dextran sodium sulfate (DSS)-induced colitis in mice and further clarify its mechanism. Materials and methodsThe ulcerative colitis model induced by DSS was successfully established and applied to evaluate the intervention effect after oral administration of LZD. Furthermore, the expression of key targets in inflammatory signaling pathways and intestinal tight junction proteins were investigated by enzyme-linked immunosorbent assay (ELISA) and quantitative real time polymerase chain reaction (qPCR) analysis. ResultsThe results showed that all doses of LZD could notably improve DSS-induced colon lesions, reduce histological scores, prolong colon length and increase body weight. Colonic inflammation in UC mice was significantly alleviated by inhibiting the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), reducing the yield of nitric oxide (NO) and inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and along with promoting the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10) after LZD treatment. Furthermore, LZD remarkably down-regulated the level of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) mRNA and up-regulated the expression of tight junction proteins (zonula occluden-1, occludin and claudin-1) in UC mice. ConclusionIn summary, this study indicated that LZD could notably improve UC symptoms by suppressing inflammation and ameliorating gut barrier, which provided scientific basis for its clinical application in the future.

A textual research on the spreading of Jin Gui Yu Han Jing

Jin Gui Yu Han Jing(, The Jade Case Classic of the Golden Cabinet) and Shanghan Lun(, Treatise on Febrile Diseases) have similar contents but different names, and they were handed down after being collated by the Medical Records Bureau in 1066, the third year of the Northern Song Dynasty. At present, Jin Gui Yu Han Jing is Chen Shijie's edition in the Qing Dynasty. Chen Shijie got the manuscript of Song Dynasty from He Zhuo, a scholar of Qing Dynasty, then corrected it, and published it in 1717. By searching the citations from Jin Gui Yu Han Jing in medical works from 1066 to 1717, and dividing them into two categories: direct quotation and indirect quotation, so as to investigate the spreading situation of Jin Gui Yu Han Jing since Song Dynasty. According to this, it can be inferred that Jin Gui Yu Han Jing had not been found by doctors in Yuan and Ming Dynasties.