Classic Herbal Formula Research Articles

Kai Yu Zhong Yu recipe mitigates stress-induced accelerated follicle loss in mice by regulating the interplay between apoptosis and autophagy via the SIRT1/FOXO1/3 pathway

BackgroundPsychological stress-related infertility is often attributed to a decline in both the quality and quantity of oocytes. Kai Yu Zhong Yu (KYZY) recipe, a classic herbal formula in Traditional Chinese Medicine (TCM), has been employed for centuries to address stress-related infertility. Our previous studies have demonstrated its effectiveness in counteracting the reduction in oocyte competence induced by psychological stress. PurposeTo investigate the mechanism by which KYZY mitigates the adverse effects of stress. MethodsFemale ICR mice were randomly assigned to one of five groups: control, CUMS, KYZY-H, KYZY-M, and KYZY-L. Except for the control group, the other groups underwent a six-week Chronic Unpredictable Mild Stress (CUMS) procedure. Following CUMS, the three KYZY groups were received high (38.2 g kg-1), medium (19.1 g kg-1), and low (9.6 g kg-1) doses of the KYZY recipe intragastrically for four weeks. Additionally, RNA interference was used to reduce Sirt1 expression in the ovary to assess the involvement of the SIRT1 pathway. ELISA, HE staining, follicle counting, TUNEL staining, and Western blot were conducted to explore the mechanism of KYZY in treatment of stress-related infertility. ResultsKYZY treatment significantly reduced concentrations of IL-6, IL-1β and TNF-α, reversed the loss of small follicles, and alleviated follicular apoptosis and autophagy. KYZY also elevated SIRT1/FOXO1/3 activity, reduced BAX expression, increased BCL-2 expression, and restored Beclin-1-dependent autophagy. Sirt1 silencing downregulated the activity of the SIRT1/FOXO1/3 pathway and triggered Caspase-3-mediated cleavage of Beclin-1 in mouse ovary. Conversely, Sirt1 silencing nullified the effect of KYZY recipe on inflammation and the regulation of apoptosis and autophagy. ConclusionKYZY enhances SIRT1/FOXO1/3 pathway activity, shifting the balance from apoptosis towards autophagy to safeguard oocyte capacity against the effects of psychological stress.

Huanglian Jiedu Decoction Inhibits LPS-induced Neuroinflammation and Attenuates the Activation of NLRP3 Inflammasome in BV2 Cells

Background: Huanglian Jiedu decoction (HLJDD) is a classical herbal formula for treating inflammatory diseases with Traditional Chinese Medicine (TCM). However, the impacts of HLJDD on neuroinflammation and the precise mechanisms involved remain poorly understood. Purpose: In the present study, HLJDD was found to inhibit lipopolysaccharide (LPS) induced neuroinflammatory responses in BV2 microglia via regulating NLRP3 inflammasome activation. Methods: Anti-inflammatory activity was evaluated with ELISA assay and the polarization changes were observed using immunofluorescent staining. The levels of NLRP3 inflammasome activation were determined using qPCR and Western blotting. Results: The administration of HLJDD successfully countered LPS-induced neuroinflammatory responses by attenuating microglial activation and fostering a phenotypic conversion from the pro-inflammatory M1 to the anti-inflammatory M2. . Additionally, HLJDD treatment demonstrated inhibition of NLRP3 inflammasome activation. Conclusion: The findings of the present study may provide insights into how HLJDD could be a therapeutic drug for neuroinflammatory diseases associated with regulating NLRP3 inflammasome and microglial activation.

Kai-xin-san improves cognitive impairment in D-gal and Aβ25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage

Ethnopharmacological relevanceKai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood. Aim of the studyTo verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota. Materials and methodsAD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments. ResultsKXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant. ConclusionKXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

The Water Element, Zang-fu Kidney and Jin Gui Shen Qi Wan

The Water Element, as part of the Traditional Chinese Medicine (TCM) Five Elements, is associated with winter, coldness, darkness and the Zang-fu organs Kidney and Bladder. The TCM Kidney, encompasses far more than the Western concept of an organ which produces and excretes the waste product urine. It controls water and fluid metabolism; a primordial generator (Ming-men Fire, Essence, Jing, promotes growth, skeleton, marrow, innate constitution); Yin-Yang dynamics (innate Yin and Yang); receives Qi; life functions (sexual behavior, reproduction, neuroendocrine axis, nervous system, urinary system, manufacture Blood, acute sense of hearing, controls the 2 lower orifices, assists respiration); as well as supports good life/living (houses commitment, will power, memory). Diseases of the Kidney can manifest as congenital deficiencies, fearful attitude, pathological changes (Yin and Yang Deficiencies, chronic debilitation), and physiological deficiencies associated with senescence. Some of the more common clinical signs of Kidney (Water Element) disease include renal/reproduction disorders, lumbar pain, hind end weakness, teeth/hair loss, deafness, lassitude, neuroendocrine disorders, asthma, congenital disease and bone disorders. One of the most famous formulas to treat Kidney Yang Deficiency and decline of Ming-men Fire is the classical herbal formula Jin Gui Shen Qi Wan. The strategy of this formula is to tonify Kidney Yin to raise Kidney Yang, (since Yin and Yang are mutually dependent), with the addition of warm herbs to ignite the Fire of Ming-men. From a Chinese medical perspective, Kidney Yang Deficiency syndrome may cause endocrine system disorders, immune-deficiency, neurological, renal, and reproductive disorders. This paper will review the Zang-fu Kidney function, and the classic Chinese herbal medicine, Jin Gui Shen Qi Wan (Kidney Qi Pill from the Golden Cabinet).

A classical herbal formula alleviates high-fat diet induced nonalcoholic steatohepatitis (NASH) via targeting mitophagy to rehabilitate dysfunctional mitochondria, validated by UPLC-HRMS identification combined with in vivo experiment

BackgroundNonalcoholic steatohepatitis (NASH) has caused a significant burden on public health care systems, the economy and society. However, there has still been no officially approved pharmacotherapy for NASH. It has been suggested that oxidative stress and mitochondrial dysfunction play vital roles in NASH pathological progression. Shugan Xiaozhi (SG) formula, as a kind of classical herbal formula, was shown to attenuate NASH. PurposeThis study aimed to explore the potential mechanisms of SG formula treating NASH. Study design and methodsUltra-high-performance liquid chromatography-high resolution mass spectrometry combined with bioinformatics analysis was applied to explore the therapeutic targets and main components of SG formula. Moreover, in vivo NASH model was utilized to confirmed the therapeutic effects of SG formula. Molecular docking analysis and further validation experiments were conducted to verify the results of bioinformatics analysis. ResultsThe in vivo experiments confirmed SG formula significantly attenuated hepatic pathological progression and relieved oxidative stress in high-fat diet (HFD) induced - NASH model. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) combined with bioinformatics analysis expounded the components of SG formula and revealed the mitochondrial regulation mechanism of SG formula treating NASH. Further in vivo experiments validated that SG formula could alleviate oxidative stress by rehabilitating the structure and function of mitochondria, which was strongly related to regulating mitophagy. ConclusionIn summary, this study demonstrated that SG formula, which could attenuate NASH by regulating mitochondria and might be a potential pharmacotherapy for NASH.

Investigation of the mechanism of action of simiao pill against gout using network pharmacology and experimental validation

BackgroundGout is a chronic disease of deposition of monosodium urate crystals, characterised by hyperuricaemia and gouty arthritis, plaguing the whole world. Simiao Pill (SMP), a classic herbal formula, has been extensively used to treat arthritic symptoms in clinical practice in China for centuries. The action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of gout. However, the pharmacological mechanisms of SMP still remain vague to date. Hypothesis/PurposeIn this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypouricemic mechanisms of SMP. Study designAt first, we collected putative targets of SMP based on Traditional Chinese Medicine Systems Pharmacology Database databases, and relevant targets of gout were summarised by four searching database, including Disgenet, therapeutic target database, Online Mendelian Inheritance in Man, and Gene Cards. The putative targets of SMP and known therapeutic targets of gout built an interaction network, so the networks of compound targets and disease-targets were obtained soon. Then, the protein–protein interactions analysis and molecular docking verification were established. Finally, the key genes were used to find the biological pathway and explain the therapeutic mechanism by genome ontology and kyoto encyclopaedia of genes and genomes analysis. ResultsIn our study, 30 hypouricemic components and 600 hypouricemic targets of SMP were filtrated based on an online network database. Then the component-target interaction network was constructed, 10 key components and 15 key targets were further obtained. Docking studies indicated that the bio-active compounds could stably bind the pockets of target proteins. Go enrichment and and kyoto encyclopaedia of Genes and genomes pathway analysis indicated that SMP had a strong integration with gout and hyperuricemia, which might significantly contribute to multiple therapeutic effect. ConclusionsIn summary, this study used systems pharmacology to demonstrate the main components and mechanism of SMP in treating gout. Moreover, the work provided a scientific basis for the further effect research of SMP and its monomer components, but also provided a new therapeutic strategy in gout.

Exploring the possible mechanism(s) underlying the nephroprotective effect of Zhenwu Decoction in diabetic kidney disease: An integrated analysis

BackgroundDiabetic kidney disease (DKD) is one of the major chronic microvascular complications of diabetes and the main cause of end-stage renal failure. Zhenwu Decoction (ZWD), an ancient classic herbal formula in Chinese medicine, has been clinically used for the treatment of kidney disease in China for many years. However, there is currently limited research investigating the application of ZWD in the treatment of DKD and the underlying chemical and biochemical mechanisms involved. Therefore, in the present study, we aimed to identify active components in ZWD and unravel the possible mechanism(s) of action for ZWD in treating DKD. MethodsThe protective effect of ZWD against DKD was evaluated utilizing an in vitro model of diabetic renal proximal tubulopathy. The major chemical components from ZWD were identified by LC-MS/MS. Drug targets were predicted by submitting the SMILES (Simplified Molecular Input Line Entry System) of the compounds to SEA (Similarity Ensemble Approach) search server and SwissTargetPrediction. The differentially expressed genes (DEGs) of the disease were collected and integrated from GeneCards. The constructions of “Compounds-potential targets interaction” (CTI) network and Protein-Protein Interaction (PPI) network, as well as topology analysis were conducted by Cytoscape. Gene Ontology (GO) enrichment and Metacore pathway enrichment analysis were also performed. Lastly, molecular docking and experimental studies were adopted to validate the core target and identify an active component(s) of ZWD. ResultsWe demonstrated that the ZWD extract could significantly rescue the palmitic acid (PA) and high glucose-induced apoptotic cell death in HK-2 cells, and the cytoprotection was accompanied by decreases in the extent of reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ATP depletion. Fifty-seven compounds in the aqueous extract of ZWD were identified by LC-MS. The results of PPI analysis showed that top hub genes involved epidermal growth factor receptor (EGFR), Signal Transducer and Activator of Transcription 3 (STAT3), Serine/Threonine Kinase 1 (AKT1), Vascular Endothelial Growth Factor A (VEGFA) and Fibroblast Growth Factor 2 (FGF2). Pathway enrichment analysis revealed the involvement of S1P1 receptor signaling and EGFR pathways. The results of molecular docking analysis showed that albiflorin has a high binding affinity to EGFR. Albiflorin could also exert protective effects in an HK-2 cell model of DKD, which may be related to the inhibition of the high glucose/high lipid-induced EGFR and Akt phosphorylation. ConclusionZWD has been shown to be effective in ameliorating cell death in an experimental model of DKD. The beneficial effect of ZWD against DKD was associated with the interactions between the active ingredients and the hub genes, such as EGFR, STAT3, AKT1, and VEGF-A. Albiflorin may be one of the active components responsible for the nephroprotective effect in ZWD.

Tibetan medicine Qi-Sai-Er-Sang-Dang-Song Decoction inhibits TNF-α-induced rheumatoid arthritis in human fibroblast-like synoviocytes via regulating NOTCH1/NF-κB/NLRP3 pathway.

Qi-Sai-Er-Sang-Dang-Song Decoction (QSD, ཆུ་སེར་སེང་ལྡེང་སུམ་ཐང་།), a Tibetan classical herbal formula, is commonly used in Tibetan hospital preparation for the treatment of rheumatoid arthritis (RA). Its efficacy is to relieve inflammation, dispel cold, remove dampness, and alleviate pain. However, its anti-RA mechanism is still unclear. This study aimed to investigate the effect of QSD on rheumatoid arthritis and explore its anti-inflammatory mechanism against human fibroblast-like synoviocytes (HFLSs) by regulating the notch family of receptors (NOTCH1)/Nuclear factor-κB (NF-κB)/nucleotide-binding (NLRP3) pathway. We used ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS) to identify the chemical composition of QSD. Then, HFLSs were exposed to drug-containing serum. The effect of QSD drug-containing serum on HFLS viability was detected using the cell counting kit-8 (CCK-8) assay. Next, we explored the anti-inflammatory effect of QSD using enzyme-linked immunosorbent assay (ELISA) for inflammatory factors, such as interleukin-18 (IL-18), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The expression of NOTCH-related proteins, a member of the NOTCH1, Cleaved NOTCH1, hairy and enhancer of split-1 (HES-1), NF-κB p65, NF-κB pp65, NLRP3, and delta-like 1 (DLL-1), was examined using western blotting. Furthermore, the relative mRNA expression levels of NOTCH1, NF-κB p65, NLRP3, DLL-1, and HES-1 were detected using real-time quantitative (RT-qPCR). To explore the mechanism underlying the anti-RA effect of QSD, we the used the NOTCH signaling pathway inhibitor LY411575 and transfection with a NOTCH1 siRNA. In addition, we employed immunofluorescence to determine the expression of HES-1 and NF-κB p65 in vitro. Our results revealed that QSD ameliorated inflammation in HFLSs. Compared with the model group, the QSD drug-containing serum group had obviously down-regulated levels of IL-18, IL-1β, and IL-6. Consistently, the CCK-8 results showed that the QSD drug-containing serum had no obvious toxicity towards HFLSs. Moreover, both LY411575 and siNOTCH1, QSD could reduce NOTCH1, NLRP3, and HES-1 protein expression levels, and LY411575 could significantly inhibit the expression levels of NF-κB p65, NF-κB pp65, and Cleaved NOTCH1 (p<0.05). siNOTCH1 could also suppress the expression of DLL-1. The RT-qPCR results indicated that QSD could downregulate the relative mRNA expression levels of NOTCH1, NF-κB p65, NLRP3, DLL-1, and HES-1 in HFLSs (p<0.05). In the immunofluorescence experiment, the fluorescence intensities of HES-1 and NF-κB p65 in HFLSs were found to decrease after exposure to QSD drug-containing serum (p<0.05). Ultimately, 44 chemical components were detected in QSD using UPLC-Q-TOF-MS. This study reveals that the QSD can markedly ameliorate inflammation induced by TNF-α on HFLS. The effect of QSD on HFLS may be exerted by inhibition of the NOTCH1/NF-κB/NLRP3 signaling pathway.

Network pharmacology and molecular docking prediction, combined with experimental validation to explore the potential mechanism of Qishen Yiqi pills against HF-related cognitive dysfunction

Ethnopharmacological relevanceQishen Yiqi Pills (QSYQ) is a classical herbal formula for treating heart failure (HF) and has potential efficacy in improving cognitive function. The latter is one of the most common complications in patients with HF. However, there is no study on treating HF-related cognitive dysfunction by QSYQ. Aims of the studyThe study aims to investigate the effect and mechanism of QSYQ on treating post-HF cognitive dysfunction based on network pharmacology and experimental validation. Materials and methodsNetwork pharmacology analysis and molecular docking was used to explore endogenous targets of QSYQ in treating cognitive impairment. Ligation of the anterior descending branch of the left coronary artery and sleep deprivation (SD) were used to induce HF-related cognitive dysfunction in rats. The efficacy and potential signal targets of QSYQ were then verified by functional evaluation, pathological staining, and molecular biology experiments. Results384 common targets were identified by intersecting QSYQ ‘compound targets’ and ‘cognitive dysfunction’ disease targets. KEGG analysis showed these targets were enriched to the cAMP signal, and four marks responsible for regulating the cAMP signal were successfully docked with core compounds of QSYQ. Animal experiments demonstrated that QSYQ significantly ameliorated cardiac function and cognitive function in rats suffering from HF and SD, inhibited the reduction of cAMP and BDNF content, reversed the upregulation of PDE4 and downregulation of CREB, suppressed the loss of neurons, and restored the expression of synaptic protein PSD95 in the hippocampus. ConclusionThis study clarified that QSYQ could improve HF-related cognitive dysfunction by modulating cAMP-CREB-BDNF signals. It provides a rich basis for the potential mechanism of QSYQ in the treatment of heart failure with cognitive dysfunction.

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. &quot;Dyspnea after sweating&quot; 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. &quot;Mild fever&quot; 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.

Systematic analysis on the mechanism of Zhizi-Bopi decoction against hepatitis B via network pharmacology and molecular docking.

Zhizi-Bopi decoction (ZZBPD) is a classic herbal formula with wide clinical applications in treating liver diseases including hepatitis B. However, the mechanism needs to be elucidated. Chemical components of ZZBPD were identified by ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF-MS). Then we used network pharmacology to identify their potential targets. Network construction, coupled with protein-protein interaction and enrichment analysis was used to identify representative components and core targets. Finally, molecular docking simulation was conducted to further refine the drug-target interaction. One hundred and forty-eight active compounds were identified in ZZBPD, targeting 779 genes/proteins, among which 174 were related to hepatitis B. ZZBPD mainly influences the progression of hepatitis B through the hepatitis B pathway (hsa05161) via core anti-HBV targets (AKT1, PIK3CA, PIK3R1, SRC, TNF, MAPK1, and MAPK3). Enrichment analysis indicated that ZZBPD can also potentially regulate lipid metabolism and enhance cell survival. Molecular docking suggested that the representative active compounds can bind to the core anti-HBV targets with high affinity. The potential molecular mechanisms of ZZBPD in hepatitis B treatment were identified using network pharmacology and molecular docking approaches. The results serve as an important basis for the modernization of ZZBPD.

Electroacupuncture Combined with A Classic Herbal Formula in The Treatment of Type 2 Diabetes: A Case Report

This article presents the case report of a 47-year-old man who was diagnosed with Type 2 diabetes and a high hemoglobin A1C level, 26%. He wanted to be treated by Traditional Chinese Medicine (acupuncture and Chinese herbs) to improve his health and decrease his level of blood sugar. The goal of the treatment is to reduce the level of hemoglobin A1C to 7%, as requested by his family doctor. Outcomes: For 4 months, electroacupuncture was done once a week in combination with the classic herbal formula of Huang-Lian-Jie-Du-Tang which was taken three times a day in the form of tea, the result of which was the patient’s level of hemoglobin A1C dropped from 26% to 7%. Conclusion: This case shows that electroacupuncture combined with the classic herbal formula HLJDT not only effectively reduces blood sugar and the hemoglobin A1C level, but it also significantly improves the subjective symptoms, helps patients to reduce the doses of medication, and prevents the progression of Type 2 diabetes.

In Silico and In Vitro studies of taiwan chingguan yihau (NRICM101) on TNF-α/IL-1β-induced human lung cells.

COVID-19 pandemic has been a global outbreak of coronavirus (SARS-CoV-2 virus) since 2019. Taiwan Chingguan Yihau (NRICM101) is the first traditional Chinese medicine (TCM) classic herbal formula and is widely used for COVID-19 patients in Taiwan and more than 50 nations. This study is to investigate in silico target fishing for the components of NRICM101 and to explore whether NRICM101 inhibits cytokines-induced normal human lung cell injury in vitro. Our results showed that network prediction of NRICM101 by a high throughput target screening platform showed that NRICM101 has multiple functions that may affect cytokine regulation to prevent human lung cell injury. In addition, NRICM101 revealed protective effects against TNF-α/IL-1β-induced normal human lung HEL 299 cell injury through JNK and p38MAPK kinase signaling. Next-generation sequencing (NGS) analysis of NRICM101 on TNF-α/IL-1β-injured HEL 299 cells indicated that inflammatory pathway, cell movement of macrophages, cellular infiltration by macrophages, and Th1/Th2 immuno-regulation pathways were included. Thus, NRICM101 is a therapeutic agent, and it can improve COVID-19 syndrome to confer beneficial effects through multiple targeting and multiple mechanisms.

Wen Dan Tang: A Potential Jing Fang Decoction for Headache Disorders?

Background: Chinese herbal medicine is considered relatively safe, inexpensive, and easily accessible. Wen Dan Tang (WDT), a Jing Fang ancient classical Chinese herbal formula with a broad indication profile has been used for several centuries in China to treat various illnesses. Question: Are there evidence-based clinical trials that show that WDT has a significant impact on the treatment of various diseases, especially in patients with migraine and tension-type headaches (TTH)? Methods: This study is based on an online database search using PubMed, Medline, Cochrane Library, AcuTrials, Embase, Semantic Scholar, Jstor, internet research, and review of ancient and modern Chinese medical textbooks regarding WDT and its compounds. Results: There were no studies on WDT in migraine and TTH; therefore, this work gathers and describes data for every single compound in the formula. Conclusion: This study suggests that the bioactive compounds found in WDT composition show potential in treating patients with neurological, psychiatric disorders, cardiovascular diseases, metabolic syndrome, and digestive disorders. Some coherence between WDT in headache reduction and improvements in the quality of life in patients with migraines and TTH could be evaluated, showing positive results of WDT in these patients.

San-Wu-Huang-Qin decoction attenuates tumorigenesis and mucosal barrier impairment in the AOM/DSS model by targeting gut microbiome

BackgroundA classic herbal formula San-Wu-Huang-Qin (SWHQ) decoction has been widely used in clinical practices to prevent and treat colorectal cancer (CRC) for years, but its anti-tumorigenic properties and the underlying mechanisms remain undetermined. PurposeThe present study used a CRC mouse model to clarify whether and how SWHQ suppresses tumorigenesis. MethodsDifferent doses of SWHQ were gavaged to the AOM/DSS model mice to examine its anti-tumor efficacy in comparison with the positive control drug Aspirin. The underlying microbiota-driven anti-tumor action of SWHQ was proven with bacterial manipulations by fecal microbial transplantation (FMT) in vivo and anaerobic culturing in vitro. ResultsSWHQ decoction dose-dependently reduced colonic tumor numbers/loads of AOM/DSS models and suppressed their disease activity index scores. SWHQ also recovered epithelial MUC2 secretion and colonic tight junction protein (ZO-1 and claudin1) expression in the mouse model. Such inhibitory impact on tumorigenesis and mucosal barrier impairment was found to be associated with modulation of gut dysbiosis, particularly for suppressing lipopolysaccharide (LPS) producers. The FMT experiment confirmed the substantial contribution of SWHQ-reshaped microbiota to anti-tumor function and mucosal barrier protection. Moreover, LPS-activated TLR4/NF-κB signaling and its downstream pro-inflammatory factors were significantly suppressed in the colon of SWHQ-treated models and SWHQ-reshaped microbiota recipients. ConclusionsWe demonstrated that the SWHQ effectively inhibited tumorigenesis and protect mucosal barrier in CRC at least partially by targeting gut microbiota. This study provides scientific basis for the clinical usage of SWHQ in CRC intervention and prevention.

Integrated analysis of the chemical-material basis and molecular mechanisms for the classic herbal formula of Lily Bulb and Rehmannia Decoction in alleviating depression

BackgroundLily Bulb and Rehmannia Decoction (LBRD), is a traditional Chinese formula that has been shown to be safe and effective against depression; however, its material basis and pharmacological mechanisms remain unknown.MethodsHere, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and high-performance liquid chromatography (HPLC) were used to identify the chemical spectrum and qualitatively identify the major active ingredients in the LBRD standard decoction, respectively. Subsequently, we assessed the behavior, neuronal function and morphology, neurotransmitter levels, hypothalamic–pituitary–adrenal (HPA)-axis associated hormones, inflammatory cytokine levels, and miRNA/mRNA expression alterations in an in vitro/vivo depression model treated by the LBRD standard decoction. Finally, miRNA/mRNA regulatory networks were created through bioinformatics analysis, followed by functional experiments to verify its role in LBRD standard decoction treatment.ResultsA total of 32 prototype compounds were identified in the LBRD standard decoction, and the average quality of verbascoside in the fresh lily bulb decoction, fresh raw Rehmannia juice, and the LBRD standard decoction were 0.001264%, 0.002767%, and 0.009046% (w/w), respectively. Administration of the LBRD standard decoction ameliorated chronic unpredictable mild stress (CUMS)-induced depression-like phenotypes and protected PC12 cells against chronic corticosterone (CORT)-induced injury. The levels of neurotransmitter, cytokine, stress hormones and neuronal morphology were disrupted in the depression model, while LBRD standard decoction could work on these alterations. After LBRD standard decoction administration, four differentially expressed miRNAs, rno-miR-144-3p, rno-miR-495, rno-miR-34c-5p, and rno-miR-24-3p, and six differentially expressed mRNAs, Calml4, Ntrk2, VGAT, Gad1, Nr1d1, and Bdnf overlapped in the in vivo/vitro depression model. Among them, miR-144-3p directly mediated GABA synthesis and release by targeting Gad1 and VGAT, and miR-495 negatively regulated BDNF expression. The LBRD standard decoction can reverse the above miRNA/mRNA network-mediated GABA and BDNF expression in the in vivo/vitro depression model.ConclusionCollectively, the multi-components of the LBRD standard decoction altered a series of miRNAs in depression through mediating GABAergic synapse, circadian rhythm, and neurotrophic signaling pathway etc., thereby abolishing inhibitory/excitatory neurotransmitter deficits, recovering the pro-/anti-inflammatory cytokine levels and regulating the HPA-axis hormone secretion to achieve balance of the physiological function of the whole body.

Wuzi Yanzong Pill, A classical herbal formula, exhibits therapeutic potential in treating Parkinson's disease

Wuzi Yanzong Pill(WYP) has a potential therapeutic effect on Parkinson's Disease(PD) mice, but the effect to ERS-mediated apoptosis pathway in PD were not studied. To determine the therapeutic effect of WYP on PD mice and explore its mechanism.

Systematic analysis of the mechanism of Xiaochaihu decoction in hepatitis B treatment via network pharmacology and molecular docking

Hepatitis B (HB) is a globally prevalent infectious disease caused by the HB virus. Xiaochaihu decoction (XCHD) is a classic herbal formula with a long history of clinical application in treating HB. Although the anti-HB activity of XCHD has been reported, systematic research on the exact mechanism of action is lacking. Here, a network pharmacology-based approach was used to predict the active components, important targets, and potential mechanism of XCHD in HB treatment. Investigation included drug-likeness evaluation; absorption, distribution, metabolism, and elimination (ADME) screening; protein-protein interaction (PPI) network construction and cluster analysis; Gene Ontology (GO) analysis; and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation. Molecular docking was adopted to investigate the interaction between important target proteins and active components. Eighty-seven active components of XCHD and 155 anti-HB targets were selected for further analysis. The GO enrichment and similarity analysis results indicated that XCHD might perform similar or the same GO functions. Glycyrrhizae Radix (GR), one of the seven XCHD herbs, likely exerts some unique GO functions such as the regulation of interleukin-12 production, positive regulation of interleukin-1 beta secretion, and regulation of the I-kappaB/NF-kappaB complex. The PPI network and KEGG pathway analysis results showed that XCHD affects HB mainly through modulating pathways related to viral infection, immunity, cancer, signal transduction, and metabolism. Additionally, molecular docking verified that the active compounds (quercetin, chrysin, and capsaicin) could bind with the key targets. This work systematically explored the anti-HB mechanism of XCHD and provides a novel perspective for future pharmacological research.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction

Ethnopharmacological relevanceHuoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RationaleTo further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. Materials and methodsThe chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). ResultsThe results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. ConclusionHuoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCβ signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Effect of Gegen Qinlian Decoction on Hepatic Gluconeogenesis in ZDF Rats with Type 2 Diabetes Mellitus Based on the Farnesol X Receptor/Ceramide Signaling Pathway Regulating Mitochondrial Metabolism and Endoplasmic Reticulum Stress.

Background Type 2 diabetes mellitus (T2DM) is a kind of disorder of glucose and lipid metabolism with the main clinical manifestation of long‐term higher blood glucose level than the normal value. Farnesol X receptor (FXR)/ceramide signaling pathway plays an important role in regulating cholesterol metabolism, lipid homeostasis, and the absorption of fat and vitamins in diet. Gegen Qinlian Decoction (GQD) is a classical herbal formula, which has a good clinical therapeutic effect on diabetes-related metabolic syndrome. Objective To investigate the effect of Gegen Qinlian Decoction (GQD) on hepatic gluconeogenesis in obese T2DM rats based on the FXR/ceramide signaling pathway regulating mitochondrial metabolism and endoplasmic reticulum stress (ERS). Methods ZDF (fa/fa) rats were fed with high-fat diet to establish the T2DM model; GQD was given to T2DM model rats by gavage; changes of the general state and body weight of rats were recorded; fasting blood glucose was detected; blood insulin, blood ceramide, glycosylated hemoglobin in blood, acetyl CoA in liver mitochondria, and bile salt lyase in intestinal tissue were detected by ELISA. The content of T-β-MCA in blood was detected by LC-MS; the content of glycogen in liver tissue was detected by PAS staining; the expression of FXR, Sptlc2, and Smpd3 in ileum tissue, P-PERK, ATF6α, GRP78 BIP, and P-IRE1 in the liver, and CS and PC protein in liver mitochondria was detected by immunohistochemistry and western blot assay. The mRNA expression levels of FXR, Sptlc2, and Smpd3 in the ileum, PERK, ATF6α, GRP78 BIP, and IRE1 in the liver, and CS and PC in liver mitochondria were detected by qRT-PCR. Results GQD can improve the general state of T2DM rats, slow down their weight gain, reduce the levels of fasting blood glucose, fasting insulin, glycosylated hemoglobin, blood ceramide, bile salt hydrolase in intestinal tissue, and acetyl CoA in liver mitochondria of T2DM rats, and increase the contents of liver glycogen and T-β-MCA in blood of T2DM rats. At the molecular level, GQD can inhibit the expression levels of FXR, Sptlc2, and Smpd3 in the ileum of T2DM rats and the protein and mRNA expression levels of oxidative stress-related factors in the liver. At the same time, GQD can increase the expression of CS and reduce the expression of PC in liver mitochondria of T2DM rats. Conclusion GQD can inhibit the FXR/ceramide signaling pathway, regulate endoplasmic reticulum stress, enhance the CS activity of liver mitochondria, reduce the acetyl CoA level and PC activity of liver mitochondria, inhibit hepatic gluconeogenesis, protect islet β-cells, and control blood glucose.