Rhizoma Atractylodis Research Articles

Fibroblastic reticular cells and type 3 innate lymphoid cells in Peyer’s patches: Target cell candidates for inulooligosaccharides in hochuekkito formula containing Atractylodis rhizoma

AbstractAimInulooligosaccharides in a Kampo formula, hochuekkito, have been shown to participate in the regulation of the pulmonary immune system. Difference in chain length distribution of the oligosaccharides strongly affects their immunopharmacological activities. This phenomenon cannot be explained by bifidogenic activity and/or short‐chain fatty acids produced by intestinal microflora from the oligosaccharides. Effects of intermediate‐size inulooligosaccharides, which have a similar chain length distribution as the oligosaccharides obtained from hochuekkito containing Atractylodis rhizoma, were analyzed on immunocompetent cells in Peyer’s patches.MethodsEffect of intermediate‐size inulooligosaccharide preparation (degree of polymerization (d.p.) 3–15) on mRNA expression of genes of markers and functional molecules of stromal cells and type 3 innate lymphoid cells (ILC3) in Peyer’s patches was analyzed.ResultsOral administration of intermediate‐size inulooligosaccharide preparation significantly up‐regulated expression of mRNAs of genes of not only marker molecules of fibroblastic reticular cells (FRC) and ILC3 but also immunological factors for positive and negative regulatory functions of FRC in addition to genes of auto‐immune regulator (AIRE), DEAF‐1 transcription factor, and some AIRE‐dependent tissue‐related antigens (TRA).ConclusionFRC and ILC3 are suggested to be target cell candidates in Peyer’s patches for inulooligosaccharides in hochuekkito formula containing Atractylodis rhizoma.

Transdermal Administration of Volatile Oil from Citrus aurantium-Rhizoma Atractylodis Macrocephalae Alleviates Constipation in Rats by Altering Host Metabolome and Intestinal Microbiota Composition.

Background The Citrus aurantium- (ZhiShi, ZS-) Rhizoma Atractylodis Macrocephalae (BaiZhu, BZ) pairs are often found in herbal formulas for constipation. The volatile oils of ZS and BZ (ZBVO) have good pharmacological activity against constipation, but the mechanism for treatment of slow transit constipation (STC) remains unclear. Method A rat model using diphenoxylate tablets was constructed to investigate if transdermal administration of ZBVO would mediate intestinal microorganisms and fecal metabolites and improve STC symptoms. The regulatory effects of ZBVO at 0.15, 0.30, and 0.60 mL kg−1 d−1 on STC rats were assessed by measuring fecal water content, intestinal propulsion rate, histopathology, expression of gastrointestinal hormones, brain and intestinal peptides, and inflammatory factors. The changes in intestinal flora of STC rats were analyzed by 16S rRNA gene sequencing. Moreover, the untargeted fecal metabolomics analysis was performed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-Q-TOF-MS) technology. Results The results showed that ZBVO had a modulating effect on STC by increasing the fecal water content and intestinal propulsion rate. Transdermal administration of ZBVO decreased serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) and increased the levels of gastrin (GAS) and substance P (SP). In addition, ZBVO increased 5-hydroxytryptamine (5-HT) levels and decreased vasoactive intestinal peptide (VIP) levels in colon and hippocampus tissues. The results of intestinal microbiota showed that ZBVO improved the diversity and abundance of intestinal microbiota and changed the community composition by decreasing Romboutsia and increasing Proteobacteria, Allobaculum, and Ruminococcaceae. And the feces metabolomics found that nicotinate and nicotinamide metabolism, purine metabolism, citrate cycle (TCA cycle), pyruvate metabolism, arachidonic acid metabolism, pyrimidine metabolism, and primary bile acid biosynthesis were modulated. Conclusion These findings suggest that ZBVO can alleviate STC symptoms by promoting intestinal peristalsis, increasing fecal water content, regulating gastrointestinal hormone level, reducing the inflammatory response, and regulating brain and intestinal peptides after transdermal administration. And structural changes in the intestinal microbiota are closely related to host metabolism and intestinal microbiota destroyed in STC modeling could be significantly improved by the ZBVO, which provides a reference for the development of aromatic drug macrohealth products.

Analysis of Clinical Value and Therapeutic Effect of Rhizoma Pinelliae, Rhizoma Atractylodis Macrocephalae and Rhizoma Gastrodiae Decoction on Hypertension, Vertigo, Phlegm and Turbidity Obstruction

Analysis of Clinical Value and Therapeutic Effect of Rhizoma Pinelliae, Rhizoma Atractylodis Macrocephalae and Rhizoma Gastrodiae Decoction on Hypertension, Vertigo, Phlegm and Turbidity Obstruction

Atractylodes lancea Rhizoma Attenuates DSS-Induced Colitis by Regulating Intestinal Flora and Metabolites.

Atractylodes lancea (Thunb.) DC. is a herb widely used traditionally for the treatment of gastrointestinal diseases such as gastric ulcer, spleen deficiency, and diarrhea. In China, people fry raw A. lancea (SCZ) together with wheat bran to make bran-fried A. lancea (FCZ). Ancient Chinese texts have documented that FCZ can enhance the function of regulating the intestines and stomach. Nevertheless, the effect and mechanism of SCZ and FCZ on ulcerative colitis (UC) are still unclear. The aim of this study was to compare the therapeutic effects of SCZ and FCZ and their mechanisms on dextran sulfate sodium (DSS)-induced UC in mice. The chemical constituents of SCZ and FCZ were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with six reference compounds. The effects of SCZ and FCZ were investigated based on their effects on weight loss, disease activity index (DAI) score, colon length shortening, goblet cell loss, and pathological changes using the colons from a mouse model of DSS-induced UC. The effects of SCZ and FCZ on levels of the inflammatory cytokines (tumor necrosis factor-[Formula: see text], interleukin-6, interleukin-1[Formula: see text], mucoprotein (MUC2), tight protein (ZO-1, occludin), and the activation of macrophages were determined using immunohistochemistry (IHC) and immunofluorescence (IF). 16s RNA sequencing technology was used to detect the composition of the intestinal flora in each group. Nontargeted metabonomics was used to detect the serum metabolite levels of mice in each group. Pearson analysis was used to determine the correlation between the intestinal flora, metabolites, and pathological indices. Reverse transcription-polymerase chain reaction was used to detect the genes of different metabolite-related enzymes. A pseudogerm free (PGF) mouse model was used to verify whether the effect of SCZ and FCZ in UC depends on the regulation of intestinal flora. SCZ and FCZ could inhibit weight loss and decrease the DAI score, colon length shortening, goblet cell loss, and the extent of pathological changes in the colons of mice with DSS-induced colitis. Moreover, SCZ and FCZ inhibited the decrease in MUC2, ZO-1, occludin, production of pro-inflammatory factors, and activation of pro-inflammatory macrophages in colonic tissue. The effect of FCZ was better than that of SCZ. SCZ and FCZ not only inhibited the abundance of harmful bacteria and increased the abundance of beneficial bacteria, but also regulated the metabolism of disease-related metabolites such as amino acid and cholesterol metabolism. Both preparations inhibited the gene expression (Slc6A7, PRODH, Sdsl, HMGCR, SREBP-2) of different metabolite-related enzymes. In the PGF mouse model, the above effects were not observed. Rhizoma Atractylodes was effective in alleviating DSS-induced UC in mice, and FCZ was found to be superior to SCZ. The mechanism of action of FCZ and SCZ is mainly related to the regulation of intestinal flora and their associated metabolites.

Network pharmacology-based study of the anti-oxidative mechanism of san miao wan in treatment of arthritis

San Miao Wan (SMW) is a traditional Chinese medicine (composed of Cortex phellodendri, Rhizoma atractylodes, and Radix cyathulae) widely used in China to treat arthritis; however, its underlying mechanism remains unknown. We established the target gene library of SMW and performed gene ontology enrichment analysis of related target genes. The component-target protein-protein interaction (PPI) network of SMW and the disease-target PPI network of arthritis were merged to form a core PPI network. Finally, the anti-oxidative effect of SMW for treating arthritis was evaluated in a rat arthritis model induced by sodium urate. The results showed that R. atractylodes contained four active components with 68 target proteins, R. cyathulae contained two active components and 139 target proteins, and C. phellodendri contained eight active components and 275 target proteins. The target genes of R. cyathulae were highly related to the synthesis and metabolism of reactive oxygen species, while target genes of R. atractylodes and C. phellodendri were highly related to the circulatory system. The component-target PPI network of SMW and the disease-target PPI network of arthritis predominantly overlapped. In vivo, SMW effectively reduced knee swelling induced by sodium urate, decreased serum malondialdehyde levels, and increased serum superoxide dismutase levels. In conclusion, the therapeutic effects of SMW in arthritis are associated with its anti-oxidative properties.

Network pharmacology-based study of the anti-oxidative mechanism of san miao wan in treatment of arthritis

San Miao Wan (SMW) is a traditional Chinese medicine (composed of Cortex phellodendri, Rhizoma atractylodes, and Radix cyathulae) widely used in China to treat arthritis; however, its underlying mechanism remains unknown. We established the target gene library of SMW and performed gene ontology enrichment analysis of related target genes. The component-target protein-protein interaction (PPI) network of SMW and the disease-target PPI network of arthritis were merged to form a core PPI network. Finally, the anti-oxidative effect of SMW for treating arthritis was evaluated in a rat arthritis model induced by sodium urate. The results showed that R. atractylodes contained four active components with 68 target proteins, R. cyathulae contained two active components and 139 target proteins, and C. phellodendri contained eight active components and 275 target proteins. The target genes of R. cyathulae were highly related to the synthesis and metabolism of reactive oxygen species, while target genes of R. atractylodes and C. phellodendri were highly related to the circulatory system. The component-target PPI network of SMW and the disease-target PPI network of arthritis predominantly overlapped. In vivo, SMW effectively reduced knee swelling induced by sodium urate, decreased serum malondialdehyde levels, and increased serum superoxide dismutase levels. In conclusion, the therapeutic effects of SMW in arthritis are associated with its anti-oxidative properties.

The Immuno-Modulatory Activities of Pentaherbs Formula on Ovalbumin-Induced Allergic Rhinitis Mice via the Activation of Th1 and Treg Cells and Inhibition of Th2 and Th17 Cells.

Allergic rhinitis (AR) is a highly prevalent allergic disease induced by immunoglobulin (Ig) E-mediated hypersensitivity reaction at the nasal epithelium against inhaled allergens. Previous studies have demonstrated that Pentaherbs formula (PHF), a modified herbal formula comprising five herbal medicines (Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis), could suppress various immune effector cells to exert anti-inflammatory and anti-allergic effects in allergic asthma and atopic dermatitis. The present study aimed to further determine the anti-inflammatory activities of PHF in an ovalbumin (OVA)-induced AR BALB/c mouse model. Nasal symptoms such as sneezing and nose rubbing were recorded and the serum total IgE and OVA-specific IgG1, as well as interleukin (IL)-4, IL-5, IL-10, IL-13, chemokines CXCL9 CXCL10, and tumor necrosis factor (TNF)-α concentrations in nasal lavage fluid (NALF) were measured during different treatments. Effects of PHF on the expression of inflammatory mediators in the sinonasal mucosa were quantified using real-time QPCR. PHF was found to suppress allergic symptoms, infiltration of inflammatory cells, and hyperplasia of goblet cells in the nasal epithelium of the OVA-induced AR mice. PHF could reduce OVA-specific IgG1 level in serum, and TNF-α and IL-10 in nasal lavage fluid (NALF), significantly up-regulate the splenic regulatory T (Treg) cell level, increase the Type 1 helper T cell (Th1)/Type 2 helper T cell (Th2) ratio, and reduce the Th17 cells (all p < 0.05). PHF could also alleviate in situ inflammation in sinonasal mucosa of OVA-induced AR mice. In conclusion, oral treatment of PHF showed immuno-modulatory activities in the OVA-induced AR mice by regulating the splenic T cell population to suppress the nasal allergy symptoms and modulating inflammatory mediators, implicating that PHF could be a therapeutic strategy for allergic rhinitis.

Safety of Oriental Medical Therapy: Drug Fever of Herbal Medicine and Procedure-related Fever

Objectives: Drug fever and procedure-related fever are the causes of nosocomial fever. Oriental medicine has been practiced in Asia and is now being practiced as an alternative medicine in western countries. No data are available on the incidence of drug fever and procedure-related fever in oriental medical hospitals (OMHs). The aim of this study was to identify the incidence of drug fever related to oriental herbal medicine and oriental medical procedure-related fever.Methods: This was a retrospective study at one OMH of a university medical institute in Seoul, Korea, conducted from June 2006 to June 2013.Results: Overall, 95 episodes of drug fever occurred among 10880 patients treated with herbal medicine (0.89%). Peak body temperature was 38.37±0.58 ℃, and the fever lasted for 1.0 day (range 1.0-17.0 days). Eosinophilia was found in 15 patients (15.79%) and 8 patients developed toxic hepatitis (8.42%). Five patients had a drug-related skin rash (5.26%). The most common ingredients of the herbal medicines associated with drug fever were licorice, Angelica gigas root, and white Atractylodes rhizome. In total, 16 episodes of procedure-related fever (0.20%) occurred in 8125 patients treated with oriental medical procedures. The peak body temperature was 38.26±0.51 ℃, and the fever lasted for 1.0 day (range 1.0-3.0 days). Among various oriental medical procedures, moxibustion was the most common procedure related to fever, followed by acupuncture.Conclusions: The incidence of drug fever and procedure-related fever in oriental medicine is not high compared with the incidence in western medicine.

Database mining and animal experiment-based validation of the efficacy and mechanism of Radix Astragali (Huangqi) and Rhizoma Atractylodis Macrocephalae (Baizhu) as core drugs of Traditional Chinese medicine in cancer-related fatigue

Ethnopharmacological relevanceIn China, Traditional Chinese medicine (TCM) is often used as the main therapy for cancer-related fatigue (CRF). However, there is limited evidence to prove its therapeutic effect and mechanism. Aim of the studyWe aimed to provide a basis for the therapeutic effect of TCM for CRF. Materials and methodsWe performed a meta-analysis to investigate the efficacy of TCM treatment for CRF. Through frequency statistics and association rule mining, we screened the core Chinese medicine components, Astragalus mongholicus Bunge., root (Radix astragali, Huangqi) and Atractylodes macrocephala Koidz., rhizome (Rhizoma atractylodis macrocephalae, Baizhu). We then used animal experiments to verify the effectiveness of these two TCMs and changes in related indicators in mice. Relevant molecular mechanisms were explored through network pharmacological analysis. ResultsTwenty-four randomised control trials (RCTs) involving 1865 patients were included in the meta-analysis. TCM produced more positive effects on CRF than standard therapy alone. Radix astragali and Rhizoma atractylodis macrocephalae, as the core drug pair for the treatment of CRF, enhanced the physical fitness of mice; reduced abdominal circumference, level of inflammatory factors, and tumour weight; and increased body weight and blood sugar. Network pharmacology analysis showed that the mechanism of action of Radix astragali and Rhizoma atractylodis macrocephalae on CRF mainly involved compounds, such as quercetin, kaempferol and luteolin, acting through multiple targets, such as Protein kinase B α (AKT1), Tumour necrosis factor (TNF), and Interleukin-6 (IL-6). These molecules regulate cytokines, cancer signalling, and metabolic pathways and confer an anti-CRF effect. ConclusionsTCM may be a promising therapy to relieve CRF in cancer patients. Our research may provide a reference for the clinical application of TCM for treating CRF.

Physico-chemical characteristics and aflatoxins production of Atractylodis Rhizoma to different storage temperatures and humidities

This study aimed to investigate the characteristics, moisture contents, chemical fingerprints changes and aflatoxins accumulation of Atractylodis rhizoma during storage, further to determine the optimum temperature and relative humidity conditions. Based on the suitable temperature (20–40 °C) and relative humidity (80–95%), 13 different temperature and humidity conditions were set up by the central composite design-response surface methodology (CCD-RSM) for Aspergillus flavus. After inoculation with Aspergillus flavus by artificial infection, A. rhizoma samples were stored under normal conditions and 13 different temperature and relative humidity levels. By taking the changes of characteristics, the contents of moisture, chemical fingerprints and aflatoxins as the evaluation indexes for A. rhizoma with or without Aspergillus flavus fungi to optimize the optimal storage conditions. After storage for 10 days, the color of A. rhizoma was deepened, the water content and chemical composition increased, and some unknown components were detected. The susceptible condition for aflatoxins production in A. rhizoma was identified at temperature 22–37 °C and relative humidity over 87.5%. Thus, the suitable storage conditions for A. rhizoma should be controlled at temperature below 20 °C and relative humidity less than 85%. This paper screened out the optimum temperature and humidity for the storage of A. rhizoma. Then, the storage specification for A. rhizoma was proposed, lying technical and data support for the scientific preservation of other food or herbs.

Comparative pharmacokinetics, intestinal absorption and urinary excretion of six alkaloids from herb pair Phellodendri Chinensis cortex-Atractylodis Rhizoma.

Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.

Analysis on application law of dampness-removing traditional Chinese medicines in treatment of coronavirus disease 2019

ObjectiveCoronavirus Disease 2019 (COVID-19) has been diagnosed as an epidemic disease characterized by cold and dampness pathogens in TCM clinic. Due to many Chinese medicines with different functions were used in the treatment of COVID-19, it is very important to find the law of application of damp-removing traditional Chinese medicine with high frequency application, with view to providing a reference for the use and research of Chinese medicine to further control the pandemic. MethodsThe publicly released diagnosis and treatment programs issued by the National Health Commission and Health Commission of provinces, autonomous regions and municipalities, and Chinese herbs prescription information in these were collected, a database was established, and Excel and Graphpad 8.0 software were used to analyze the frequency of use of various Chinese medicines, the frequency and property characters including five flavors (bitter, pungent, sweet, sour, and salty) and four natures (warm, hot, cool, and cold) and channel tropisms of Chinese medicine for removing dampness. ResultsA total of 137 prescriptions of Chinese medicine for treating COVID-19 were collected, including 178 TCMs showing functions of resolving phlegm, relieving cough and asthma, resolving dampness, clearing damp and inducing dieresis, clearing heat, tonifying deficiency, and relieving exterior syndrome, in which the TCMs with the first four functions that we called the dampness-removing TCMs, accounted for 35.78%. Also a number of TCMs in the rest functions showed removing-dampness. The first four functions were divided into subfunctions including aromatic resolvingdampness, clearing heat and drying dampness, drying dampness and tonifying spleen qi, drying dampness and removing phlegm, inducing diuresis and relieving swelling, inducing diuresis and relieving exterior syndrome. Among them, the most frequently used TCMs was Ephedrae Herba, followed by Citri Reticulatae Pericarpium, Pogostemonis Herba, Pinelliae Rhizoma, Poria, Scutellariae Radix, and Atractylodis Rhizoma. The property character analysis in the dampness-removing TCMs showed that bitter and pungent were largely present and sour and astringent were absent, warm and hot were dominant; And the lung, spleen, stomach, large intestine, bladder were main channel tropisms. ConclusionDampness-removing TCMs are the first important type of traditional Chinese medicine to be considered in the treatment of COVID-19 in Chinese medicine. The application of dampness-removing TCMs in the treatment of COVID-19 needs to be combined with its application law. This study may provide meaningful and useful information on further research to investigate the effective compounds from the dampness-removing Chinese medicine with high frequency application, and also provide a reference for the clinical treatment of COVID-19 accurately against dampness evil with dampness-removing traditional Chinese medicines.

Atractylenolide I inhibits antibiotic-induced dysbiosis of the intestinal microbiome.

BackgroundAtractylenolide I (AT-I) is an active component that is isolated from Rhizoma Atractylodis macrocephalae and it exerts anti-apoptotic, anti-oxidant, and anti-coagulant properties, and has been widely applied in the treatment of cardiovascular and cerebrovascular diseases in China. This study aimed to investigate the effects and possible mechanism of AT-I on intestinal dysbacteriosis in a mouse model.MethodsMice dysbacteriosis models were established and treated with AT-I, and the intestinal microbiome of the mice were compared. Using antibiotics-induced bacterial elimination in an intestinal dysbacteriosis-associated xenograft model, the gut microbiota-mediated anti-tumor mechanism was investigated.ResultsThe intestinal microbiome was changed in the dysbacteriosis mice compared to the control mice, and AT-I could affect the intestinal microbiome of the dysbacteriosis mice. Manipulation of gut bacteria in the intestines of the dysbacteriosis-associated xenograft model further confirmed that the inhibition of tumor progression by AT-I was mediated by the gut microbiota, and that the underlying mechanism involves down-regulation of TLR4/MyD88/NF-κB signaling. AT-I repressed the phosphorylation of p65-NF-κB as well as the downstream cytokines, IL-6 and IL-1β, in dysbacteriosis mice.ConclusionsAT-I may inhibit dysbacteriosis by affecting the intestinal microbiome via the regulation of TLR4/MyD88/NF-κB signaling. The present study provides a basis for the application of AT-I as an alternative medication for treating gastrointestinal disorders.

LC-ESI-MS/MS Simultaneous Analysis Method Coupled with Cation-Exchange Solid-Phase Extraction for Determination of Pyrrolizidine Alkaloids on Five Kinds of Herbal Medicines.

BackgroundPyrrolizidine alkaloids (PAs) are naturally occurring plant toxins associated with potential hepatic and carcinogenic diseases in humans and animals. The concern over PAs has increased as the consumption of herbal medicines has increased.ObjectiveThis study aimed to develop and validate a sensitive analytical method to determine 28 PAs in five herbal medicines using liquid chromatography (LC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS). Additionally, this study identified and quantified the amount of PAs in 10 samples of each herbal medicine.MethodsThe pretreatment in the proposed LC-MS/MS analysis comprised solvent extraction using 0.05M H2SO4 in 50% methanol and clean-up step using an mixed-mode cationic exchange (MCX)-solid-phase extraction (SPE) cartridge. The PA contents in herbal medicines were measured by using the developed method.ResultsThe proposed method had recoveries ranging from 72.5–123.7% for the Atractylodis Rhizoma Alba, 70.6–151.7% for Alba Chrysanthmi Flos, 80.6–130.9% for Leonuri Herba, 70.3–122.9% for Gastrodiae Rhizoma, and 67.1–106.9% for Glycyrrhizae Radix. Even though a few samples showed recoveries in unsatisfactory values, the proposed method indicated entirely sufficient recoveries and precision in most samples. In monitoring results, only Leonuri Herba contained two PAs, which indicated Retrorsine (4/10) of 84.7–120.9 μg/kg and Senkirkine (10/10) of 60.9–170.7 μg/kg.ConclusionThe results obtained from this study demonstrate that the proposed method is fit for purpose to determine 28 PAs in herbal medicines. Therefore it could serve as a regulatory method capable of being used for controlling the risks of PAs in certain medicinal plants and dietary supplements.HighlightsAn LC-MS/MS method for the determination of 28 pyrrolizidine alkaloids in herbal medicines was developed and validated through this study. The proposed method is considered as an useful method for monitoring pyroolizidine alkaloids in herbal medicines.

Atractylodis rhizoma water extract attenuates fructose-induced glomerular injury in rats through anti-oxidation to inhibit TRPC6/p-CaMK4 signaling

BackgroundAtractylodis rhizoma, an aromatic herb for resolving dampness, is used to treat Kidney-related edema in traditional Chinese medicine for thousands years. This herb possesses antioxidant effect. However, it is not yet clear how Atractylodis rhizoma prevents glomerular injury through its anti-oxidation. PurposeBased the analysis of Atractylodis rhizoma water extract (ARE) components and network pharmacology, this study was to explore whether ARE prevented glomerular injury via its anti-oxidation to inhibit oxidative stress-driven transient receptor potential channel 6 (TRPC6) and its downstream molecule calcium/calmodulin-dependent protein kinase IV (CaMK4) signaling. MethodsLiquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze ARE components. Network pharmacology analysis was preliminarily performed. Male Sprague-Dawley rats were given 10% fructose drinking water (100 mL/d) for 16 weeks. ARE at 720 and 1090 mg/kg was orally administered to rats for the last 8 weeks. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity in rat kidney cortex were detected, respectively. In rat glomeruli, redox-related factors forkhead box O3 (FoxO3), SOD2 and catalase (CAT), podocyte slit diaphragm proteins podocin and nephrin, cytoskeleton proteins CD2-associated protein (CD2AP) and α-Actinin-4, as well as TRPC6, p-CaMK4 and synaptopodin protein levels were analyzed by Western Blotting. SOD2 and CAT mRNA levels were detected by qRT-PCR. Results36 components were identified in ARE. Among them, network pharmacology analysis indicated that ARE might inhibit kidney oxidative stress. Accordingly, ARE up-regulated nuclear FoxO3 expression, and then increased SOD2 and CAT at mRNA and protein levels in glomeruli of fructose-fed rats. It reduced H2O2 and MDA levels, and increased SOD activity in renal cortex of fructose-fed rats. Subsequently, ARE down-regulated TRPC6 and p-CaMK4, and up-regulated synaptopodin in glomeruli of fructose-fed rats. Furthermore, ARE increased podocin and nephrin, as well as CD2AP and α-Actinin-4, being consistent with its reduction of urine albumin-to-creatinine ratio and improvement of glomerular structure injury in this animal model. ConclusionsThese results suggest that ARE may prevent glomerular injury in fructose-fed rats possibly by reducing oxidative stress to inhibit TRPC6/p-CaMK4 signaling and up-regulate synaptopodin expression. Therefore, ARE may be a promising drug for treating high fructose-induced glomerular injury in clinic.

Identification of different bran-fried Atractylodis Rhizoma and prediction of atractylodin content based on multivariate data mining combined with intelligent color recognition and near-infrared spectroscopy

Unclear established standard of bran-fried Atractylodis Rhizoma (BFAR), a commonly used drug in Traditional Chinese Medicine (TCM), compromised its clinical efficacy. In this study, we explored the correlation between color and near-infrared spectroscopy (NIR) feature with content of atractylodin, then established a rapid recognition model for the optimal degree of processing for BFAR preparation. The results of the Pearson analysis indicated that the color values were significantly and positively correlated with atractylodin content. The back propagation artificial neural network algorithm and cluster analysis revealed the color of different BFAR could be accurately divided into three categories; subsequently, the color range for the optimal degrees of stir-frying was established as follows: R[red value (105.79–127.25)], G[green value(75.84–89.64)], B[blue value(33.33–42.73)], L[Lightness (81.26–95.09)].Using NIR, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and cluster analysis, three types of BFAR were accurately identified. The prediction model of atractylodin content was established using partial least squares regression analysis. The R2 of the validation set was 0.9717 and the root mean square error was 0.026. In the color judgment model, the processing degree of 8 batches of BFAR from the market is inferior. According to the NIR judgment model, the processing degree of all samples from the market is inferior. In conclusion, the best fire degree of BFAR can be identified quickly and accurately based on our established model. It is a potential method for quality evaluation of Chinese Materia Medica processing.

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis

Ethnopharmacological relevanceErmiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named “Tong Feng”, which is described as “ache in bones and joints” with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. Aim of the studyPresent study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). Materials and methodsRat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine, phellodendrine, magnoflorine, jatrorrhizine, berberrubine, palmatine, and tetrahydropalmatine, in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. ResultsPC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. ConclusionsThe VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.

Atractylenolide III reduces depressive- and anxiogenic-like behaviors in rat depression models

Atractylenolide III, a major component of the atractylodes macrocephala Koidz, derived from the rhizoma atractylodes, has been reported to produce various pharmacological effects including anti-aging, anti-inflammation, anti-tumor, and other effects. Growing evidence suggests that proinflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α, are increased in depressed patients. The present study was aimed at investigating the antidepressant- and anxiolytic-like effects of atractylenolide III in lipopolysaccharide (LPS) challenge and chronic unpredictable mild stress (CUMS) rat model. We found that 30 mg/kg of atractylenolide III administered by oral gavage for 14 days, significantly reduced the immobility time in a forced swimming test (FST), but did not alter the number of crossings in an open field test (OFT), respectively. The results indicated that atractylenolide III has an antidepressant-like effect without affecting locomotor activity. We then used the LPS-induced depression model to assess the effects of atractylenolide III on behaviors in FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT). Interestingly, in addition to the antidepressant-like effects, 30 mg/kg of atractylenolide III also produced an anxiolytic-like effect. To further identify the antidepressant- and anxiolytic-like effects of atractylenolide III, we used the CUMS model with 28 consecutive days of the atractylenolide III treatment, followed by the SPT, FST, and NSFT. Atractylenolide III prevented CUMS-induced depressive- and anxiety-like behaviors in rats. To illustrate the underlying possible mechanisms of action of atractylenolide III, we measured the proinflammatory cytokines levels. The results showed that atractylenolide III decreased the proinflammatory cytokines levels in the hippocampus of CUMS exposed rats. In summary, our findings demonstrated that atractylenolide III produces antidepressant- and anxiolytic-like effects in rats, and these effects appear to be mediated by inhibition of hippocampal neuronal inflammation.

Extraction and separation, structure analysis and biological activity of polysaccharides from Atractylodis Rhizoma

Atractylodis Rhizoma(AR) is a traditional Chinese medicinal material for food and medicine, with the functions of eli-minating dampness, strengthening the spleen, expelling wind evil and dispersing cold. AR contains a variety of compounds, including sesquiterpenoids, alkynes, triterpenoids, aromatic glycosides, polysaccharides and so on. At present, the researches on AR mainly focus on volatile components, with relatively fewer researches on non-volatile components. Polysaccharide from Atractylodis Rhizoma(ARP) is an important material basis among non-volatile components for the efficacy. Due to its many biological activities such as immunomodulatory activity, anti-tumors, anti-virus and anti-oxidation, ARP has certain research value and potential. The diversity of the polysaccharide structure is the basis for biological functions, but it also increases the difficulty of carbohydrate research. The research on the extraction, separation, purification, structure and activity of ARP is in the preliminary exploration stage, still with many shortcomings. Herein, recent advancements in the extraction, purification, structural characteristics and biological activities of ARP were summarized in this article to provide scientific reference for the in-depth systematic research of ARP and the development of AR resources.

Efficacy and safety of Chinese herbal medicine Jianpi formulas for atopic dermatitis: Evidence from 11 randomized controlled trials.

Jianpi formulas have been widely used to treat atopic dermatitis (AD) by traditional Chinese medicine (TCM) practitioners, but the efficacy and safety need further evaluation. A meta-analysis of randomized controlled trials was performed to assess the efficacy and tolerability of Jianpi formulas for AD. We searched the following databases up to October 2020: PubMed, Embase, China National Knowledge Infrastructure database (CNKI), and Wanfang database. All randomized controlled trials (RCTs) evaluated Jianpi formulas add-on effect for AD were included for meta-analysis. The primary outcome was minor remission. Secondary outcomes include complete remission, marked remission, and decrease of SCORAD. Totally eleven studies were included. Nine studies were included in qualitative analysis and seven were included in quantitative analysis. The common herbs were poria, glycyrrhiza uralensis, rhizoma atractylodis, atractylodes macrocephala, and semen coicis. The Jianpi formulas add-on therapy showed consistent higher effectiveness rate in complete remission (RR1.528, 95%CI 1.176-1.984. p<0.01; Q=2.31, I2 =0%), marked remission (RR 1.388, 95% CI 1.234-1.562. p<0.01; Q=3.682, I2 =0%), and minor remission (RR 1.170, 95% CI 1.105-1.239, p<0.01; Q=14.355, I2=44.27%). The decrease of the scoring atopic dermatitis (SCORAD) in Jianpi formulas was significantly higher than in control group (SMD=0.671, 95% CI 0.018 to 0.937). Jianpi formulas were generally well tolerated, with no significantly increased risk of adverse events (AE). The combinations of Jianpi formulas showed moderate positive add-one effects in AD patients. Further well-designed clinical trials are needed to evaluate long-term effect of this therapy.