Traditional Chinese Herbal Formula Research Articles

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery.

Gastroesophageal reflux disease (GERD) is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage. Wendan Decoction (WDD) is a traditional Chinese herbal formula used to treat various gastrointestinal disorders, such as gastritis, functional dyspepsia, and irritable bowel syndrome. Mosapride, a prokinetic agent, functions as a selective 5-hydroxytryptamine 4 agonist, enhancing gastrointestinal motility. To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery. Eighty patients with GERD were randomly divided into treatment (receiving WDD combined with mosapride) and control (receiving mosapride alone) groups. The treatment was conducted from January 2021 to January 2023. The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire (RDQ). The secondary outcomes were improved esophageal motility (measured using esophageal manometry), gastric emptying (measured using gastric scintigraphy), and quality of life [measured via the Short Form-36 (SF-36) Health Survey]. The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters, such as lower esophageal sphincter pressure, peristaltic amplitude, and peristaltic velocity compared to the control group. The treatment group showed significantly higher gastric emptying rates and SF-36 scores (in both physical and mental domains) compared to the control group. No serious adverse effects were observed in either group. WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery. It can improve GERD symptoms, esophageal motility, gastric emptying, and the quality of life of patients. Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

HuoXueTongFu formula induces M2c macrophages via the MerTK/PI3K/AKT pathway to eliminate NETs in intraperitoneal adhesion in mice

Ethnopharmacological relevanceHuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. Aim of the studyIn surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. MethodsIn this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. ResultsHXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. ConclusionHXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.

Zixue Powder attenuates septic thrombosis via reducing neutrophil extracellular trap through blocking platelet STING activation

Ethnopharmacological relevanceMicrothrombosis is commonly seen in sepsis and COVID-19. Zixue Powder (ZXP) is a traditional Chinese herbal formula with the potential to treat microvascular and infectious diseases. However, the role and mechanism of ZXP in sepsis-associated thrombosis remain unclear. Aim of the studyInvestigating the therapeutic effectiveness and underlying mechanisms of ZXP in septic thrombosis. Materials and methodsZXP's compositions were examined with UPLC-QTOF-MS. The efficacy of ZXP on sepsis-induced thrombosis was assessed through various methods: liver tissue pathology was examined using hematoxylin-eosin staining, platelet count was determined by a blood cell analyzer, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum tissue factor (TF), thromboxane B2 (TXB2), D-Dimer, and plasminogen activator inhibitor-1 (PAI-1). Neutrophil extracellular traps (NETs) were localized and expressed in liver tissues by immunofluorescence, and the number of NETs in peripheral blood was evaluated by ELISA, which measured the quantity of cf-DNA and MPO-DNA in serum. Platelet P-selectin expression and platelet-neutrophil aggregation were measured by flow cytometry, and plasma P-selectin expression was measured by ELISA. Furthermore, the mechanism of the stimulator of interferon genes (STING) signaling pathway in ZXP's anti-sepsis thrombosis effect was investigated using the STING agonist, Western blot experiments, and immunoprecipitation experiments. ResultsUPLC-QTOF-MS identified 40 chemical compositions of ZXP. Administration of ZXP resulted in significant improvements in liver thrombosis, platelet counts, and levels of TXB2, TF, PAI-1, and D-Dimer in septic rats. Moreover, ZXP inhibited NETs formation in both liver tissue and peripheral blood. Additionally, ZXP decreased the levels of P-selectin in both platelets and plasma, as well as the formation of platelet-neutrophil aggregates, thereby suppressing P-selectin-mediated NETs release. Immunoprecipitation and immunofluorescence staining experiments revealed that ZXP attenuated P-selectin secretion by inhibiting STING-mediated assembly of platelet soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complex, ultimately preventing inhibition of NETs formation. ConclusionOur study showed that ZXP effectively mitigates platelet granule secretion primarily through modulation of the STING pathway, consequently impeding NET-associated thrombosis in sepsis. These findings offer valuable insights for future research on the development and application of ZXP.

Homotherapy for Heteropathy: A Molecular Mechanism of Poria Sini Decoction for Treatment of Liver Cancer and Chronic Heart Failure.

Poria sini decoction (PSD), a significant traditional Chinese herbal formula, is effective in liver cancer (LC) and chronic heart failure (CHF); however, little is known about its concurrent targeting mechanism. Methods. This study analyzed the potential molecular mechanism of PSD against the two distinct diseases using network pharmacology approaches, including multidatabase search, pharmacokinetic screening, network construction analysis, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and molecular docking to elaborate the active components, signaling pathways, and potential mechanisms of PSD in the treatment of both LC and CHF. Results. A total of 155 active components and 193 potential targets in PSD were identified. Bioinformatics analysis revealed that quercetin, isorhamnetin, and naringenin, etc. may be potential candidate agents. TNF, AKT1, and IL6, etc. could become potential therapeutic targets. TNF-α, NF-κB, PI3K-AKT, and TRP signaling pathways might play an important role in PSD against LC and CHF. Molecular docking results showed that most screened active compounds could embed itself into target proteins with a high binding affinity, and the hydrogen bonds number ≥3 indicated a more stable conformation of the compounds and target proteins. Overall, quercetin and isorhamnetin were the main active components, and TNF and AKT1 were the primary targets for PSD treatment of LC and CHF. Conclusions. This study illustrated that quercetin contained in PSD played an important role in the treatment of LC and CHF by acting on the key gene of TP53 and downregulating the PI3K-AKT signaling pathway.

Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice

BackgroundAutoimmune hepatitis (AIH) is an immune-mediated hepatic disease associated with intense complications. AIH is more common in females and needs effective drugs to treat. Guizhi Fuling Wan (GZFLW) is a traditional Chinese herbal formula used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH. MethodsThe tandem MS-based analysis was used to identify secondary metabolites in GZFLW. Therapeutic effects of GZFLW were tested in a concanavalin A (Con A)-induced AIH model in mice. Ethnopharmacological mechanisms underlying the antiapoptotic, antioxidant, and immunomodulatory protective effects were determined. ResultsOral administration of GZFLW attenuates AIH in a Con A-induced hepatotoxic model in vivo. The tandem MS-based analysis identified 15 secondary metabolites in GZFLW. The Con A-induced AIH syndromes, including hepatic apoptosis, inflammation, reactive oxygen species accumulation, function failure, and mortality, were significantly alleviated by GZFLW in mice. Mechanistically, GZFLW restrained the caspase-dependent apoptosis, restored the antioxidant system, and decreased pro-inflammatory cytokine production in the livers of Con A-treated mice. Besides, GZFLW repressed the Con A-induced hepatic infiltration of inflammatory cells, splenic T cell activation, and splenomegaly in mice. ConclusionsOur findings demonstrate the applicable potential of GZFLW in treating AIH. It prompts further investigation of GZFLW as a treatment option for AIH and possibly other hepatic diseases.

The Effects of Traditional Chinese Herbal Dietary Formula on the Ability of Daily Life and Physical Function in Elderly Patients with Mild Cognitive Impairment.

We aimed to examine the association of traditional Chinese herbal dietary formulas with ability of daily life and physical function in elderly patients with mild cognitive impairment. The current study included 60 cases of elderly patients with mild cognitive impairment from Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine and Hongkou District, Shanghai. The participants were randomly divided into two groups: group A (herbal dietary formula group, consisting of Alpiniae Oxyphyllae Fructus, Nelumbinis plumula, Chinese Yam, Poria cocos, and Jineijin), 30 cases, and group B (vitamin E), 30 cases, treatment for 3 months. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA) and Mini-Mental State Examination (MMSE); body function was measured using the Chinese Simplified Physical Performance Test (CMPPT), including stand static balance, sitting-up timing, squat timing, and six-meter walk timing. Daily life based on ability was measured by grip strength and the Activity of Daily Living Scale (ADL). The lower the scores of the above items, the poorer the disease degree, except for ADL: the lower the score, the higher the self-care ability. After 3 months of treatment, the two-handed grip strength of both the herbal dietary formula group and vitamin E group increased; the ADL, sitting-up timing, squatting timing, and six-meter walking timing decreased after medication, being statistically significantly different (p < 0.05). The two-handed grip strength of group A increased significantly, and the ADL, sitting-up timing, squatting timing, and six-meter walking timing decreased distinctly compared with the vitamin E group. There was a statistically significant difference (p < 0.05). The scores of MMSE, MOCA, total CMPPT, and standing static balance of the herbal dietary formula group increased after medication. The difference was statistically significant (p < 0.05). The vitamin E group's MMSE and MOCA scores, CMPPT total scores, and standing resting balance scores did not change significantly after medication (p > 0.05). In summary, a traditional Chinese herbal dietary formula can improve body and cognitive function in patients with MCI, and the curative effect is better than that of vitamin E. Traditional Chinese herbal dietary formulas can improve the daily life quality of MCI patients, which has clinical application value.

Xuefu Zhuyu decoction promotes synaptic plasticity by targeting miR-191a-5p/BDNF-TrkB axis in severe traumatic brain injury

BackgroundXuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal formula known for its ability to eliminate blood stasis and improve blood circulation, providing neuroprotection against severe traumatic brain injury (sTBI). However, the underlying mechanism is still unclear. PurposeWe aim to investigate the neuroprotective effects of XFZYD in sTBI from a novel mechanistic perspective of miRNA-mRNA. Additionally, we sought to elucidate a potential specific mechanism by integrating transcriptomics, bioinformatics, and conducting both in vitro and in vivo experiments. MethodsThe sTBI rat model was established, and the rats were treated with XFZYD for 14 days. The neuroprotective effects of XFZYD were evaluated using a modified neurological severity score, hematoxylin and eosin staining, as well as Nissl staining. The anti-inflammatory effects of XFZYD were explored using quantitative real-time PCR (qRT-PCR), Western blot analysis, and immunofluorescence. Next, miRNA sequencing of the hippocampus was performed to determine which miRNAs were differentially expressed. Subsequently, qRT-PCR was used to validate the differentially expressed miRNAs. Target core mRNAs were determined using various methods, including miRNA prediction targets, mRNA sequencing, miRNA-mRNA network, and protein-protein interaction (PPI) analysis. The miRNA/mRNA regulatory axis were verified through qRT-PCR or Western blot analysis. Finally, morphological changes in the neural synapses were observed using transmission electron microscopy and immunofluorescence. ResultsXFZYD exhibited significant neuroprotective and anti-inflammatory effects on subacute sTBI rats' hippocampus. The analyses of miRNA/mRNA sequences combined with the PPI network revealed that the therapeutic effects of XFZYD on sTBI were associated with the regulation of the rno-miR-191a-5p/BDNF axis. Subsequently, qRT-PCR and Western blot analysis confirmed XFZYD reversed the decrease of BDNF and TrkB in the hippocampus caused by sTBI. Additionally, XFZYD treatment potentially increased the number of synaptic connections, and the expression of the synapse-related protein PSD95, axon-related protein GAP43 and neuron-specific protein TUBB3. ConclusionsXFZYD exerts neuroprotective effects by promoting hippocampal synaptic remodeling and improving cognition during the subacute phase of sTBI through downregulating of rno-miR-191a-5p/BDNF axis, further activating BDNF-TrkB signaling.

Yunvjian decoction mitigates hyperglycemia in rats induced by a high-fat diet and streptozotocin via reducing oxidative stress in pancreatic beta cells

Ethnopharmacological relevanceYunvjian (YNJ), a traditional Chinese herbal formula first reported in Jing Yue Quan Shu, is commonly used in the clinical treatment of type 2 diabetes mellitus (T2DM). However, the mechanism by which YNJ affects T2DM remains unclear. Aim of the studyThis study aimed to assess the therapeutic effects of YNJ on T2DM and explore the potential mechanism involved. Materials and methodsHigh-performance liquid chromatography (HPLC) was used to identify the chemical compounds of YNJ. The anti-T2DM effects of YNJ were observed in a high-fat diet/streptozotocin induced rat model. The type 2 diabetic rats were prepared as follows: rats were fed a high-fat diet for four weeks and then intraperitoneally injected with a low dose (30 mg/kg) of streptozotocin. YNJ and the positive control metformin were used in these experiments. Biochemical assays were implemented to determine the fasting blood glucose, glucose tolerance, insulin sensitivity, serum lipid levels, and oxidative stress index of the pancreas. Hematoxylin-eosin (H&E) staining was used to assess histopathological alterations in the pancreas. The mechanism by which YNJ affects T2DM was evaluated in INS-1 cells treated with glucose and high sodium palmitate. YNJ-supplemented serum was used in these experiments. Methyl thiazolyl tetrazolium assays, enzyme-linked immunosorbent assays, Nile red staining, flow cytometric analysis, and Western blotting were used to assess apoptosis, insulin secretion, lipid accumulation, reactive oxygen species production, and protein levels. ResultsFive major compounds were identified in YNJ. In high-fat diet/streptozotocin-induced diabetic rats, YNJ-M notably decreased fasting blood glucose and lipid levels; ameliorated glucose tolerance, insulin sensitivity, and islet morphology; reduced Malondialdehyde levels; and restored superoxide dismutase activity in the pancreatic islets. Furthermore, the effect of YNJ-M was significantly greater than that of YNJ-L, and YNJ-H had little effect on diabetic rats. In vitro experiments revealed that YNJ-supplemented serum (10%, 15%, and 20%) dramatically suppressed apoptosis, mitigated intracellular lipid accumulation and reduced intracellular oxidative stress levels in a dose-dependent manner. Additionally, YNJ-supplemented serum increased the protein expression of Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, and superoxide dismutase 1 and inhibited the protein expression of Kelch-like ECH-associated protein 1. ConclusionYNJ ameliorates high-fat diet/streptozotocin induced experimental T2DM. The underlying mechanism involves reducing oxidative stress in pancreatic beta cells. The findings of this study provide scientific justification for the application of the traditional medicine YNJ in treating T2DM.

The Application and Pathway Regulation of Traditional Chinese Medicine in Lung Cancer Treatment: An Exploratory Review

Lung cancer is one of the cancers with the highest mortality rate. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is often diagnosed at an advanced stage with a poor prognosis. Due to the lack of effective molecular targets, the current clinical cure rate is low, and the recurrence rate is high. Recent studies have found that active components of traditional Chinese medicine and Chinese herbal formulas can inhibit the development of NSCLC through multiple pathways and targets, effectively reducing its metastasis and recurrence rates, improving treatment side effects, and compensating for the deficiencies in drug resistance. Although treatments such as surgery, radiotherapy, targeted therapy, and immunotherapy have achieved better clinical efficacy in treating lung cancer, they still have problems such as multiple complications and severe adverse reactions. In recent years, numerous basic and clinical studies have confirmed the good effects of traditional Chinese medicine in treating lung cancer. Traditional Chinese medicine has a synergistic regulatory effect through multiple components, targets, pathways, and channels. The numerous active monomeric components and complex mechanisms of action determine that there are issues such as unclear related mechanisms of action in the prevention and treatment of lung cancer by traditional Chinese medicine. There is an urgent need to elucidate the mechanisms of action of traditional Chinese medicine in intervening lung cancer from the perspective of modern medicine, and at the levels of molecular biology, network pharmacology, etc. This article systematically summarizes the research progress on the regulation of the above-mentioned signaling pathways and the expression of key protein molecules by traditional Chinese medicine monomers or formulas, aiming to clarify the mechanisms of action of traditional Chinese medicine in the progression of lung cancer, and to provide ideas and theoretical basis for the in-depth study and clinical application of traditional Chinese medicine in intervening lung cancer.

ZeXieYin formula alleviates atherosclerosis by inhibiting the MAPK/NF-κB signaling pathway in APOE−/− mice to attenuate vascular inflammation and increase plaque stability

Ethnopharmacological relevanceZexieyin formula (ZXYF), a traditional Chinese herbal formula recorded in the Huangdi Neijing to have efficacy in relieving spleen dampness and heat accumulation syndrome, which is also the key pathogenesis of atherosclerosis (AS). The efficacy has demonstrated by our previous studies. However, the intrinsic mechanism of ZXYF for treating vascular inflammation and the effect of inflammatory response on plaque are not known. Currently, plaque stabilization is crucial for the prognosis of AS. Aim of the studyOur study mainly focused on the therapeutic effects of ZXYF on high-fat diet (HFD)-induced vascular inflammation and vulnerable plaques (VP) in mice and explored its underlying mechanism. Methods and materialsMale apolipoprotein E knockout (APOE−/−) mice were fed HFD for 8 weeks to establish a VP model. During this period, the mice were also administered ZXYF, while atorvastatin (ATO) was used as a positive control. Aortic plaque area and morphology were detected by oil red staining and HE staining. Aortic plaque collagen content was detected by Masson staining. M1/M2 type macrophages were detected using immunofluorescence (IF). The study analyzed the levels of inflammation-related cytokines (IL-1β, IL-10, IL-6), MAPK/NF-κB pathway proteins, and NLRP3 inflammasomes (NLRP3, Caspase-1) using Western blot. Additionally, the levels of matrix metalloproteinase (MMP)-2 and MMP-9 and α-smooth muscle actin (α-SMA) in the aorta were analyzed using immunohistochemistry (IHC). The plaque instability index was calculated for each group using the vulnerable plaque formula. ResultsIn this study, APOE−/− mice were fed high-fat diet for 8 weeks. The results of oil-red and HE staining indicated a significant increase in the aortic plaque area of the mice, which exhibited a typical VP phenotype. ZXYF and ATO significantly improved AS plaques and prevented plaque rupture. HFD exacerbated vascular inflammation, stimulated macrophage conversion to M1-type through the MAPK/NF-κB signaling pathway, and released pro-inflammatory factors such as interleukin (IL)-1β, IL-1α, and IL-6. These factors activated NLRP3 inflammasome, leading to cellular death. However, ZXYF could reverse this trend and promote the conversion of macrophages to the anti-inflammatory M2 type. The anti-inflammatory effect of ATO was not significant. Moreover, HFD promoted the release of MMP-2 and MMP-9 from macrophages, which degraded plaque collagen, and induced a decrease in plaque SMC content, resulting in a thinning of the plaque fibrous cap. In contrast, ZXYF inhibited the decomposition of plaque collagen and increased the content of plaque smooth muscle cells (SMC) by reducing macrophage secretion of MMPs, thereby stabilizing plaques. Although ATO could reverse the decrease in plaque collagen and SMC content, its effect on MMPs was not significant. Finally, we calculated the vulnerability index to assess the overall risk of the plaque vulnerability phenotype. In line with these findings, ZXYF and ATO were able to effectively reverse the increase in the vulnerability index caused by HFD and lower the risk of adverse cardiovascular events. ConclusionOur results suggested that ZXYF could reduce inflammation and increase plaque stability by inhibiting the MAPK/NF-κB signaling pathway, which provided a theoretical basis for clinical application and subsequent research.

Chemical profiling and mechanisms of Agarikon pill in a rat model of cigarette smoke-induced chronic obstructive pulmonary disease

Background and aimAgarikon pill (AGKP), a traditional Chinese herbal formula, and has been used for chronic obstructive pulmonary disease (COPD) treatment clinically. However, the active components and exact pharmacological mechanisms are still unclear. We aimed to investigate the therapeutic effects and mechanisms of AGKP on COPD and identify the chemical constituents and active compounds. Experimental procedureThe chemical components of AGKP were identified by ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Network pharmacology analysis was performed to uncover the potential mechanism of AGKP. The efficiencies and mechanisms of AGKP were further confirmed in COPD animal models. Results and conclusionNinety compounds from AGKP, such as flavonoids, triterpenoids, saponins, anthracenes, derivatives, phenyl propionic acid, and other organic acids, were identified in our study. AGKP improved lung function and pathological changes in COPD model rats. Additionally, inflammatory cell infiltration and proinflammatory cytokine levels were markedly reduced in COPD rats administered AGKP. Network pharmacology analysis showed that the inflammatory response is the crucial mechanism by which AGKP exerts therapeutic effects on COPD rats. WB and PCR data indicated that AGKP attenuated the inflammatory response in COPD model rats. AGKP reduces the pulmonary inflammatory response through the PI3K/AKT and MAPK TLR/NF-κB signaling pathways and exerts therapeutic effects via inhibition of inflammation and mucus hypersecretion on COPD model rats.

Chinese medicine practitioners’ consensus on traditional Chinese medicine diagnostic patterns, symptoms, and herbal formulas for COVID-19 survivors: A Delphi study

IntroductionIn April 2022, the “Guidance and recommendations on Chinese Medicine Rehabilitation during COVID-19 recovery stage (pilot version)” (the CM Rehabilitation Guidance) was formulated for Hong Kong COVID-19 survivors. However, no consensus regarding traditional Chinese medicine (TCM) diagnostic patterns, symptoms, and herbal formulas in the Guidance has been reached among Hong Kong Chinese medicine practitioners (CMPs). Thus, this study aimed to establish a consensus among them as a guidance for practice. MethodsA modified Delphi method was conducted from July 28 to September 14, 2022. Each survey gathered feedback by using a five-point Likert scale and open-ended questions. Descriptive statistics for quantitative data and thematic analysis for qualitative data were used. The consensus was defined as ≥80 % level of agreement with interquartile range (IQR) ≤1. ResultsA total of 13 CMPs with clinical experience in managing COVID-19 survivors participated in the three-round Delphi survey. A final consensus was reached regarding the following: (1) the diagnostic pattern qi deficiency of the lung and spleen (median = 4; IQR = 0; level of agreement = 92.31 %) with six new suggested symptom items; (2) the diagnostic pattern dual deficiency of qi and yin (median = 4; IQR = 0.5; level of agreement = 100 %) with three new suggested symptom items; and (3) the suggested herbal formulas for these two diagnostic patterns after modification. ConclusionsThrough the three-round Delphi survey, we established a modified CM Rehabilitation Guidance for Hong Kong COVID-19 survivors. The modified Guidance based on the views of Hong Kong CMPs with frontline clinical experience in COVID-19 should be more applicable to current COVID-19 survivors.

Proteomic Analysis of Staphylococcus aureus Treated with ShangKeHuangShui.

Staphylococcus aureus (SAU) stands as the prevailing pathogen in post-traumatic infections, with the emergence of antibiotic resistance presenting formidable treatment hurdles. The pressing need is to explore novel antibiotics to address this challenge. ShangKeHuangShui (SKHS), a patented traditional Chinese herbal formula, has gained widespread use in averting post-traumatic infections, but its biological effects remain incomplete understanding. This study's primary objective was to delve into the antibacterial properties, potential antibacterial compounds within SKHS, and their associated molecular targets. In vitro SKHS antibacterial assays demonstrated that the minimum inhibitory concentration (MIC) was 8.625 mg/mL and the minimum bactericide concentration (MBC) was 17.25 mg/mL. Proteomic analysis based on tandem mass tag (TMT) showed significant changes in the expression level of 246 proteins in SKHS treated group compared to control group, with 79 proteins upregulated and 167 proteins downregulated (>1.5-fold, p < 0.05). Subsequently, thirteen target proteins related to various biological processes and multiple metabolic pathways were selected to conduct parallel reaction monitoring (PRM) and molecular docking screen. In protein tyrosine phosphatase PtpA (ptpA) docking screening, phellodendrine and obacunone can bind to ptpA with the binding energy of - 8.4 and - 8.3 kcal/mol, respectively. This suggests their potential impact on antibacterial activity by modulating the two-component system of SAU. The discovery lays a groundwork for future research endeavors for exploring new antibacterial candidates and elucidating specific active chemical components within SKHS that match target proteins. Further investigations are imperative to unveil the biological effects of these monomers and their potential synergistic actions.

Traditional Chinese Medicine formula Dai-Zong-Fang alleviating hepatic steatosis in db/db mice via gut microbiota modulation.

Introduction: Hepatic steatosis is a hepatic pathological change closely associated with metabolic disorders, commonly observed in various metabolic diseases such as metabolic syndrome (MetS), with a high global prevalence. Dai-Zong-Fang (DZF), a traditional Chinese herbal formula, is widely used in clinical treatment for MetS, exhibiting multifaceted effects in reducing obesity and regulating blood glucose and lipids. This study aims to explore the mechanism by which DZF modulates the gut microbiota and reduces hepatic steatosis based on the gut-liver axis. Methods: This study utilized db/db mice as a disease model for drug intervention. Body weight and fasting blood glucose were monitored. Serum lipid and transaminase levels were measured. Insulin tolerance test was conducted to assess insulin sensitivity. Hematoxylin and eosin (HE) staining was employed to observe morphological changes in the liver and intestine. The degree of hepatic steatosis was evaluated through Oil Red O staining and hepatic lipid determination. Changes in gut microbiota were assessed using 16S rRNA gene sequencing. Serum lipopolysaccharide (LPS) levels were measured by ELISA. The expression levels of intestinal tight junction proteins, intestinal lipid absorption-related proteins, and key proteins in hepatic lipid metabolism were examined through Western blot and RT-qPCR. Results: After DZF intervention, there was a decrease in body weight, alleviation of glucose and lipid metabolism disorders, reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and mitigation of insulin resistance in mice. DZF significantly modulated the diversity of the gut microbiota, with a notable increase in the abundance of the Bacteroidetes phylum. PICRUSt indicated that DZF influenced various functions in gut microbiota, including carbohydrate and amino acid metabolism. Following DZF intervention, serum LPS levels decreased, intestinal pathological damage was reduced, and the expression of intestinal tight junction protein occludin was increased, while the expression of intestinal lipid absorption-related proteins cluster of differentiation 36 (CD36) and apolipoprotein B48 (ApoB48) were decreased. In the liver, DZF intervention resulted in a reduction in hepatic steatosis and lipid droplets, accompanied by a decrease fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) and fatty acid transport protein 2 (FATP2). Conversely, there was an increase in the expression of the fatty acid oxidation-related enzyme carnitine palmitoyltransferase-1𝛂 (CPT-1𝛂). Conclusion: DZF can regulate the structure and function of the intestinal microbiota in db/db mice. This ameliorates intestinal barrier damage and the detrimental effects of endotoxemia on hepatic metabolism. DZF not only inhibits intestinal lipid absorption but also improves hepatic lipid metabolism from various aspects, including de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. This suggests that DZF may act on the liver and intestine as target organs, exerting its effects by improving the intestinal microbiota and related barrier and lipid absorption functions, ultimately ameliorating hepatic steatosis and enhancing overall glucose and lipid metabolism.

Intranasal administration of the essential oil from Perillae Folium ameliorates social defeat stress-induced behavioral impairments in mice

Ethnopharmacological relevancePerillae Folium, the leaves and twigs of Perilla frutescens (L.) Britton, has been included in many traditional Chinese medicine herbal formulas to treat depression. However, the precise antidepressant mechanism of the essential oil from Perillae Folium (PFEO) has not been fully investigated. Aim of the studyTo assess the effects and potential mechanisms of PFEO on depression using animal models and network pharmacology analysis. Materials and methodsPFEO was intranasally administered to a mouse model of social defeat stress (SDS). The antidepressant effects of PFEO on SDS-induced mice were evaluated using behavioral tests. Enzyme-linked immunosorbent assay (ELISA) and western blot were performed to measure the levels of depression-related biomarkers in the hippocampus and serum of the mice. The chemical compounds of PFEO were determined using gas chromatography-mass spectrometry (GC-MS). Network pharmacology and molecular docking analyses were conducted to investigate the potential bioactive components of PFEO and the mechanisms underlying the antidepressant effects. To validate the mechanisms of the bioactive compounds, in vitro models using PC12 and BV2 cells were established and the blood-brain barrier (BBB) permeability was evaluated. ResultsThe intranasal administration of PFEO suppressed SDS-induced depression in mice by increasing the time spent in the social zone and the social interactions in the social interaction test and by decreasing the immobility time in the tail suspension and forced swimming tests. Moreover, the PFEO treatment reduced the SDS-induced anxiety-like behavior, as inferred from the increased activity in the central zone observed in the open field test and in the open arms observed in the elevated plus maze test. PFEO administration recovered the SDS-induced decrease in the levels of 5-HT, NE, gamma-aminobutyric acid (GABA), and p-ERK in the hippocampus of mice. Furthermore, the increased serum corticosterone level was also attenuated by the PFEO treatment. A total of 21 volatile compounds were detected in PFEO using GC-MS, among which elemicin (15.52%), apiol (15.16%), and perillaldehyde (12.79%) were the most abundant ones. The PFEO compounds targeted 32 depression-associated genes, which were mainly related to neural cells and neurotransmission pathways. Molecular docking indicated good binding affinities between the bioactive components of PFEO (apiol, β-caryophyllene, elemicin, and myristicin) and the key targets, including ACHE, IL1B, IL6, MAOB, SLC6A2, SLC6A3, SLC6A4, and tumor necrosis factor. Among the four compounds, β-caryophyllene, elemicin, and myristicin were more effective in reducing neurotoxicity and neuroinflammation. Elemicin showed the highest BBB permeability rate. ConclusionsThis study shows the antidepressant activities of PFEO in an SDS-induced mouse model and suggests its potential mechanisms of action: regulation of the corticosterone levels, hippocampal neurotransmitters, and ERK signaling. Apiol, β-caryophyllene, elemicin, and myristicin may be the main contributors to the observed effects induced by PFEO. Further studies are needed to fully elucidate the underlying mechanisms and the main PFEO bioactive components.

Constructing a competitive endogenous RNA network of EndMT-related atherosclerosis through weighted gene co-expression network analysis.

Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction and plaque formation. Under pro-inflammatory conditions, endothelial cells can undergo endothelial-to-mesenchymal transition (EndMT), contributing to atherosclerosis development. However, the specific regulatory mechanisms by which EndMT contributes to atherosclerosis remain unclear and require further investigation. Dan-Shen-Yin (DSY), a traditional Chinese herbal formula, is commonly used for cardiovascular diseases, but its molecular mechanisms remain elusive. Emerging evidence indicates that competing endogenous RNA (ceRNA) networks play critical roles in atherosclerosis pathogenesis. In this study, we constructed an EndMT-associated ceRNA network during atherosclerosis progression by integrating gene expression profiles from the Gene Expression Omnibus (GEO) database and weighted gene co-expression network analysis. Functional enrichment analysis revealed this EndMT-related ceRNA network is predominantly involved in inflammatory responses. ROC curve analysis showed the identified hub genes can effectively distinguish between normal vasculature and atherosclerotic lesions. Furthermore, Kaplan-Meier analysis demonstrated that high expression of IL1B significantly predicts ischemic events in atherosclerosis. Molecular docking revealed most DSY bioactive components can bind key EndMT-related lncRNAs, including AC003092.1, MIR181A1HG, MIR155HG, WEE2-AS1, and MIR137HG, suggesting DSY may mitigate EndMT in atherosclerosis by modulating the ceRNA network.

Qing-Re-Chu-shi decoction ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice through anti-inflammation and immunoregulatory mechanisms

Ethnopharmacological relevanceQing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood. Aim of the studyAtopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model. Materials and methodsNetwork pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions. ResultsThe construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment. ConclusionsThe study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.

Investigation of the hypoglycemic mechanism of the ShenQi compound formula through metabonomics and 16S rRNA sequencing.

Introduction: Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by in vitro studies. However, the hypoglycemic effect and underlying mechanisms of Shenqi Compound (SQ), a traditional Chinese herbal formula, remain elusive. This study aimed to elucidate the hypoglycemic effects of SQ and explore its mechanisms of action, focusing on intestinal flora and metabolomics. Methods: A Type 2 diabetes mellitus (T2DM) rat model was established through a high-fat diet, followed by variable glucose and insulin injections to mimic the fluctuating glycemic conditions seen in diabetes. Results: An eight-week regimen of SQ significantly mitigated hyperglycemia, inflammation, and insulin resistance in these rats. Notably, SQ beneficially modulated the gut microbiota by increasing populations of beneficial bacteria, such as Lachnospiraceae_NK4A136_group and Akkermansia, while reducing and inhibiting harmful strains such as Ruminococcus and Phascolarctobacterium. Metabolomics analyses revealed that SQ intervention corrected disturbances in Testosterone enanthate and Glycerophospholipid metabolism. Discussion: Our findings highlight the hypoglycemic potential of SQ and its mechanisms via modulation of the gut microbiota and metabolic pathways, offering a theoretical foundation for the use of herbal medicine in diabetes management.

The Potential Mechanisms of Qufeng Zhitong Capsule against Rheumatoid Arthritis Based on Network Pharmacology and In Vitro Experiments.

Qufeng Zhitong capsule (QFZTC) is a traditional Chinese herbal formula with potential therapeutic efficacy in rheumatoid arthritis (RA). This study seeks to clarify the potential effects and mechanisms of QFZTC against RA. Active compounds and targets of QFZTC were retrieved from the Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID) databases. RA-related targets were searched on GeneCards and DisGeNET databases. Protein-protein interaction (PPI) network was established using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were performed on hub targets. Molecular docking was conducted on hub targets and active compounds. High-performance liquid chromatography (HPLC) was applied to characterize the active compounds in QFZTC. RA-fibroblast like synoviocytes (RA-FLSs) were cultured and treated by QFZTC-containing serum, in which proinflammatory cytokines and hub targets were detected. Cell viability was determined by cell counting kit-8 (CCK-8) assay. A total of 360 active compounds and 445 potential targets are identified for QFZTC against RA. Protein-protein interaction (PPI) network determined five hub targets, interleukin 6 (IL6), IL1B, VEGFA, JUN, and tumor necrosis factor (TNF). GO and KEGG analyses revealed that the MAPK pathway may be a critical signaling in QFZTC treating RA. Molecular docking showed that luteolin, kaempferol, and myricetin has good affinity with TNF, and they were identified by HPLC. In vitro experiments confirmed that QFZTC restrained the cell viability and inflammation in RA. This study revealed the active compounds and molecular targets for QFZTC treating RA. QFZTC is a promising drug and ameliorates RA by inhibiting inflammatory response.

Integrative Approach to Gastrointestinal Wellness: Efficacy of a Traditional Chinese Herbal Tea Formula Containing Hemp Seed

Integrative Approach to Gastrointestinal Wellness: Efficacy of a Traditional Chinese Herbal Tea Formula Containing Hemp Seed