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Phytochemical study on the roots of Achyranthes bidentata Blume led to the isolation of sixteen compounds including three new ones (1–3). Their chemical structures were determined as oleanolic acid 28-O-β-D-glucopyranoside-3-O-[β-D-glucopyranosyl-(1→3)-β-D-galactopyranoside) (1), methyl (8Z,11Z)-5,6,7-trihydroxytetradeca-8,11-dienoate (2), methyl (6E,11Z)-5,8,9-trihydroxytetradeca-6,11-dienoate (3), fulgidic acid (4), (9E,11E)-13-oxooctadeca-9,11-dienoic acid (5), (9Z,11E,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid (6), oleanolic acid 28-O-β-D-glucopyranoside-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucuronopyranoside (7), oleanolic acid 28-O-β-D-glucopyranoside-3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucuronopyranoside (8), oleanolic acid 3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucuronopyranoside (9), oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranoside (10), blumenol C glucoside (11), citroside A (12), 6S,9S-roseoside (13), ginsenoside Rg1 (14), 20-hydroxyecdysone (15), and benzyl α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside (16) by spectroscopic analysis. Compounds 1, 7 and 11–16 inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 28.03 to 54.23 µM (positive control, L-NMMA: IC50 = 35.52 µM). Compounds 14 and 15 showed anti α-glucosidase activity with IC50 values of 176.24 and 156.92 µM, respectively, compared with the positive control, acarbose, IC50 = 160.99 μM. [ABSTRACT FROM AUTHOR]

Background: Achyranthes bidentata (AR) is a traditional Chinese herb used for the treatment of hypertension and cerebral ischemia, but its pharmacological effects are not known. Aim of study: We aimed to detect and accurately identify the components and metabolites of AR in the plasma and brain tissue of Sprague Dawley rats. Methods: We employed ultrahigh performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HR-MS) to detect AR components in the plasma and brain tissue of rats. The absorption and metabolites in the plasma and brain tissue of normal control rats and rats that underwent middle cerebral artery occlusion (MCAO) were characterized and compared. Results: A total of 281 compounds, including alkaloids, flavonoids, terpenoids, phenylpropanes, sugars and glycosides, steroids, triterpenes, amino acids, and peptides, was identified in samples of Achyranthes bidentata (TCM-AR). Four types of absorbable prototype components and 48 kinds of metabolites were identified in rats in the normal control plasma group which were given AR (AR plasma group), and five kinds of metabolites were identified in rats of the normal control brain tissue group which were given AR (AR brain group). Three absorbed prototype components and 13 metabolites were identified in the plasma of rats which underwent MCAO and were given AR (MCAO + AR plasma group). Six absorbed prototype components and two metabolites were identified in the brain tissue of rats who underwent MCAO and were administered AR (MCAO + AR brain group). These results showed that, after the oral administration of AR, the number of identified components in plasma was more than that in brain tissue. The number of prototype components in the AR plasma group was higher than that in the MCAO + AR plasma group, which may indicate that metabolite absorption in rats undergoing MCAO was worse. The number of prototype components in the MCAO + AR brain group was higher than that in the AR brain group, indicating that the blood–brain barrier was destroyed after MCAO, resulting in more compounds entering brain tissue. Conclusions: UHPLC–HR-MS was used to rapidly analyze the components and metabolites of AR in the blood and brain of rats under normal and pathologic conditions, and to comprehensively characterize the components of TCM-AR. We also analyzed and compared the absorbable components and metabolites of normal rats under cerebral ischemia-reperfusion injury to explore the potential mechanism of action. This method could be applied to various Chinese herbs and disease models, which could promote TCM modernization. [ABSTRACT FROM AUTHOR]

An effective method by high‐speed countercurrent chromatography coordinated with silver nitrate for the preparative separation of sterones and triterpenoid saponins from Achyranthes bidentata Blume was developed. Methyl tert‐butyl ether/n‐butanol/acetonitrile/water (4:2:3:8, v/v/v/v) was selected for 20‐hydroxyecdysone (compound 1), chikusetsusaponin IVa methyl ester (compound 4), 2′‐glycan‐11‐keto‐pigmented saponin V (compound 5), as well as a pair of isomers of 25S‐inokosterone (compound 2) and 25R‐inokosterone (compound 3), which were further purified by silver nitrate coordinated high‐speed countercurrent chromatography. What is more, dichloromethane/methanol/isopropanol/water (6:6:1:4, v/v/v/v) was applied for calenduloside E (compound 6), 3β‐[(O‐β‐d‐glucuronopyranosyl)‐oxy]‐oleana‐11,13‐dien‐28‐oic acid (compound 7), zingibroside R1 (compound 8) and chikusetsusaponin IVa (compound 9). Adding Ag+ to the solvent system resulted in unique selectivity for 25R/25S isomers of inokosterone, which increased the complexing capability and stability of Ag+ coordinated 25S‐inokosterone, as well as the α value between them. These results were further confirmed by the computational calculation of geometry optimization and frontier molecular orbitals assay. Comprehensive mass spectrometry and nuclear magnetic resonance analysis demonstrated the structures of the obtained compounds. [ABSTRACT FROM AUTHOR]

Objectives: Oligo-/polysaccharides from Cyathula officinalis Kuan (COPs) and Achyranthes bidentata Blume (ABPs) have attracted researchers' attention in the fields of healthy food supplements and traditional Chinese medicine (Niúxī) due to their multiple bioactivities combined with their nontoxic and highly biocompatible nature. The purpose of this paper was to provide a systematic and comprehensive overview of the extraction, purification, and structural analysis methods, chemical characteristics, biological activities, and structure bioactivity relationship. Furthermore, the possible development trends and perspectives for future research, and traditional uses of Niúxī are also summarized. Methods: All the information was gathered from a library search and scientific databases. Key findings: Although COPs and ABPs are derived from different plants, they have similar structural features in type, structure, and glycosidic linkage patterns and biological activities in vivo and in vitro. However, there are differences in monosaccharide compositions, which can be used as an identification mark. Conclusions: As traditional Chinese herbal medicine, C. officinalis and A. bidentata have similar pharmacological activities. The COPs and ABP possess wide pharmacological effects such as antitumor, antioxidant, anti-osteoporosis, and anti-inflammatory. Meanwhile, the biological activity and structure–activity relationship of purified COPs and ABPs are less studied, future research should focus on them. Graphical Abstract [ABSTRACT FROM AUTHOR]

Achyranthes bidentata is always salt-processed before being prescribed for treating osteoarthritis. Yet the salt-processing parameters have not been optimized, and the specific bioactive constituents responsible for the osteoarthritis effect of salt-processed A. bidentata have not been fully elucidated. In this study, a Box–Behnken experimental design was chosen for the optimization of the salt-processing parameters of A. bidentata, including stir-frying time, concentration of brine, and soak time. Meanwhile, HPLC–Q-TOF-MS was utilized to analyze the chemical profiles of various batches of raw and salt-processed A. bidentata. The anti-inflammatory potential of nine batches of both raw and salt-processed A. bidentata was assessed via a cyclooxygenase-2 (COX-2) inhibitory assay. A gray correlation analysis was conducted to correlate the peak areas of the compounds in raw and salt-processed A. bidentata with their COX-2 inhibitory effects. Finally, the optimal salt-processing conditions are as follows: soak time: 29 min; concentration of brine: 1.8%; stir-frying time: 4.4 min. Twenty-nine compounds were identified. Eight compounds were found to have a strong positive correlation with anti-inflammatory activity, as confirmed by the COX-2 inhibitory assay. Notably, this is the first report of the COX-2 inhibitory effects of sanleng acid, stachysterone D, dihydroactinidiolide, N-cis-feruloyl-3-methoxytyramine, 9,12,13-trihydroxy-10-octadecenoic acid, azelaic acid, and dehydroecdysone. [ABSTRACT FROM AUTHOR]

The bark of Eucommia ulmoides and the roots of Achyranthes bidentata are commonly used in traditional Chinese medicine, and their pairing appears in many traditional Chinese medicine formulas as a recognized compatible unit. However, the changes and interactions of the main components of these two formulas when paired remain unclear, and there is currently no standard or method for their quality control and assessment of pharmacological effects. An optimized ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was established for the simultaneous identification of 10 components in E. ulmoides and A. bidentata using in vitro and in vivo models. Tributyltin methacrylate was the internal standard solution, and the blood samples were treated by an organic solvent precipitation method. Gradient elution was conducted on a C18 column at 25 °C with 0.1% formic acid water:acetonitrile as the mobile phase at a flow rate of 0.5 mL min−1. Dynamic multiple response monitoring was performed in negative-ion mode using an Agilent Jet Stream electrospray ionization ion source. In negative-ion detection mode, eucommiol exhibited a good response, and the isomers ginsenoside Ro and achyranthoside C could also be well separated. The developed method accurately detected the five components with a low blood content. Compared to controls, the levels of ginsenoside Ro, chikusetsusaponin Ⅳa, and achyranthoside C increased; the contents of geniposidic acid and pinoresinol diglucoside were unchanged; and the levels of eucommiol, geniposide, β-ecdysterone, genipin, and achyranthoside D decreased in vitro. In vivo , the contents of geniposidic acid, geniposide, pinoresinol diglucoside, and β-ecdysterone were reduced; the contents of eucommiol and ginsenoside Ro were unchanged; and those of achyranthoside D, chikusetsusaponin Ⅳa, and achyranthoside C increased compared to the corresponding levels in the internal control. A method for the quality control of the E. ulmoides-A. bidentata drug pair was established for the first time and the main components in 10 drug pairs could be determined simultaneously in vitro and in vivo. These findings show that the E. ulmoides and A. bidentata drug pair cause a compositional change, providing new ideas for the development of this combination to improve clinical efficacy. [ABSTRACT FROM AUTHOR]

Peanut southern blight is a fungal disease which is caused by the pathgen Sclerotium rolfsii Sacc., and seriously restricts the quality and yield of peanut. In this study, 116 strains of actinomycetes were isolated and purified from rhizosphere soil of Achyranthes bidentata by dilution coating method, and the strains that can control peanut southern blight were screened and identified. Two strains, Soil-1-5 and Soil-3-28, with good and stable antifungal activity, were screened by the plate confrontation test, and their inhibition rates were 80.43% and 92.34%, respectively. Morphological observation, physiological and biochemical tests, and 16S rRNA gene sequence analysis identified strains Soil-1-5 and Soil-3-28 as Streptomyces scabiei and Streptomyces luteogriseus, respectively. The inhibition of aseptic fermentation filtrate of antagonistic strains on plant pathogens was measured by mycelium growth rate method. The results showed that after 5 times dilution of aseptic fermentation filtrate of strains Soil-1-5 and Soil-3-28, the inhibit rates of S. rolfsii were 73.67% and 57.11%, respectively, and the two strains had different degrees of inhibition effects on the six plant pathogens including Fusarium graminearum. In addition, the two strains of aseptic fermentation filtrate also had good antagonistic effects on the sclerotinia germination and sclerotinia formation. The results of pot experiment showed that the control effects of strain Soil-1-5 and Soil-3-28 on peanut southern blight were 51.92% and 31.74%, respectively, and strain Soil-3-28 could promote the growth of peanut. In conclusion, strains Soil-1-5 and Soil-3-28 had better control efficacy on peanut southern blight, and had potential application value. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a prevalent bone metabolism disease characterized by a reduction in bone density, leading to several complications that significantly affect patients’ quality of life. The Achyranthes bidentata–Dipsacus asper (AB–DA) herb pair is commonly used in Traditional Chinese Medicine (TCM) to treat osteoporosis. This study aimed to investigate the therapeutic compounds and potential mechanisms of AB–DA using network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. Methods: Identified compounds of AB–DA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), TCM@ Taiwan Database, BATMAN-TCM, and relevant literature. The main bioactive ingredients were screened based on the criteria of “OB (oral bioavailability) ≥ 30, DL (drug-likeness) ≥ 0.18.” Potential targets were predicted using the PharmMapper and SwissTargetPrediction websites, while disease (osteoporosis)-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The PPI network and KEGG/GO enrichment analysis were utilized for core targets and pathway screening in the STRING and Metascape databases, respectively. A drug–compound–target–pathway–disease network was constructed using Cytoscape software to display core regulatory mechanisms. Molecular docking and dynamics simulation techniques explored the binding reliability and stability between core compounds and targets. In vitro and in vivo validation experiments were utilized to explore the anti-osteoporosis efficiency and mechanism of sitogluside. Results: A total of 31 compounds with 83 potential targets for AB–DA against osteoporosis were obtained. The PPI analysis revealed several hub targets, including AKT1, CASP3, EGFR, IGF1, MAPK1, MAPK8, and MAPK14. GO/KEGG analysis indicated that the MAPK cascade (ERK/JNK/p38) is the main pathway involved in treating osteoporosis. The D–C–T–P–T network demonstrated therapeutic compounds that mainly consisted of iridoids, steroids, and flavonoids, such as sitogluside, loganic acid, and β-ecdysterone. Molecular docking and dynamics simulation analyses confirmed strong binding affinity and stability between core compounds and targets. Additionally, the validation experiments showed preliminary evidence of antiosteoporosis effects. Conclusion: This study identified iridoids, steroids, and flavonoids as the main therapeutic compounds of AB–DA in treating osteoporosis. The underlying mechanisms may involve targeting core MAPK cascade (ERK/JNK/p38) targets, such as MAPK1, MAPK8, and MAPK14. In vivo experiments preliminarily validated the anti-osteoporosis effect of sitogluside. Further in-depth experimental studies are required to validate the therapeutic value of AB–DA for treating osteoporosis in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Achyranthes bidentata (AR) is a traditional Chinese herb used for the treatment of hypertension and cerebral ischemia, but its pharmacological effects are not known. Aim of study: We aimed to detect and accurately identify the components and metabolites of AR in the plasma and brain tissue of Sprague Dawley rats. Methods: We employed ultrahigh performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HR-MS) to detect AR components in the plasma and brain tissue of rats. The absorption and metabolites in the plasma and brain tissue of normal control rats and rats that underwent middle cerebral artery occlusion (MCAO) were characterized and compared. Results: A total of 281 compounds, including alkaloids, flavonoids, terpenoids, phenylpropanes, sugars and glycosides, steroids, triterpenes, amino acids, and peptides, was identified in samples of Achyranthes bidentata (TCM-AR). Four types of absorbable prototype components and 48 kinds of metabolites were identified in rats in the normal control plasma group which were given AR (AR plasma group), and five kinds of metabolites were identified in rats of the normal control brain tissue group which were given AR (AR brain group). Three absorbed prototype components and 13 metabolites were identified in the plasma of rats which underwent MCAO and were given AR (MCAO + AR plasma group). Six absorbed prototype components and two metabolites were identified in the brain tissue of rats who underwent MCAO and were administered AR (MCAO + AR brain group). These results showed that, after the oral administration of AR, the number of identified components in plasma was more than that in brain tissue. The number of prototype components in the AR plasma group was higher than that in the MCAO + AR plasma group, which may indicate that metabolite absorption in rats undergoing MCAO was worse. The number of prototype components in the MCAO + AR brain group was higher than that in the AR brain group, indicating that the blood–brain barrier was destroyed after MCAO, resulting in more compounds entering brain tissue. Conclusions: UHPLC–HR-MS was used to rapidly analyze the components and metabolites of AR in the blood and brain of rats under normal and pathologic conditions, and to comprehensively characterize the components of TCM-AR. We also analyzed and compared the absorbable components and metabolites of normal rats under cerebral ischemia-reperfusion injury to explore the potential mechanism of action. This method could be applied to various Chinese herbs and disease models, which could promote TCM modernization.

The root of Achyranthes bidentata Blume (AB) is a well-known traditional Chinese medicine for treating osteoporosis. Plenty of studies focused on the pharmacological mechanism of the whole extract; however, the contribution of different components to the anti-osteoporosis effect remains unknown. The aim of this study is to explore the anti-osteoporosis mechanism of different components of crude and salt-processed AB under the guidance of network pharmacology, metabolomics, and microbiomics. First, network pharmacology analysis was applied to constructing the compound-target-disease network of AB to provide a holistic view. Second, the anti-osteoporosis effects of the four components were evaluated in female Wistar rats. The subjects were divided into a normal group, a model group, a 17α-estradiol (E2)-treated group, a polysaccharide-component-treated groups, and a polysaccharide-knockout-component-treated groups. All the serum, urine, and feces samples of the six groups were collected after 16 weeks of treatment. Biochemical and microcomputed tomography (μCT) parameters were also acquired. Coupled with orthogonal partial least-squares discrimination analysis, one dimensional nuclear magnetic resonance (NMR) was used to monitor serum metabolic alterations. A total of twenty-two biomarkers, including lipids, amino acids, polyunsaturated fatty acids, glucose, and so on were identified for the different components-treated groups. Through pathway analysis, it is indicated that glyoxylate and dicarboxylate metabolism, glycine, serine, and threonine metabolism, alanine, aspartate, and glutamate metabolism, d-glutamine, and d-glutamate metabolism were the major intervened pathways. Levels of these biomarkers shifted away from the model group and were restored to normal after treatment with the four components. In addition, 16S rDNA sequencing demonstrated that the abundance of Anaerofilum, Rothia, and Turicibacter bacteria was positively correlated with an anti-osteoporosis effect, whereas the abundance of Oscillospira was negatively correlated. The osteoprotective effect of the polysaccharide components of crude and salt-processed AB is related to the regulation of the abundance of these gut microbiota. [ABSTRACT FROM AUTHOR]

A new isoflavonoid glycoside, achyranthoside C (1), along with two known compounds (2 and 3) were isolated from the rhizomes of Achyranthes bidentata. Compounds 1-2 were two rare natural isoflavonoid glycosides with C8 hydroxymethylene derivatization. Their structures were elucidated through comprehensive 1D and 2D NMR, UV, IR, and HRMS analyses. Bioassay results showed all the three compounds had obviously cell-protective effects against H2O2-induced H9c2 cardiomyocytes injury in a concentration -dependent manner. [ABSTRACT FROM AUTHOR]

Achyranthes root is a crude drug used as diuretic, tonic and remedy for blood stasis. Characteristic oleanolic acid saponins with a dicarboxylic acid moiety have been isolated as one of the representative constituents of this crude drug. This review focuses on the triterpene saponin constituents, especially those with a characteristic dicarboxylic acid moiety, of A. bidentata and A. fauriei. Several groups isolated the saponins and different names were given to one compound in some cases. The names of the compounds are sorted out and the stereochemistry of the dicarboxylic acid moieties are summarized. HPLC analysis of the composition of the saponin constituents and the effect of processing and extraction conditions on the composition are reviewed. Biological activities of the saponin constituents are also summarized. [ABSTRACT FROM AUTHOR]

To explore the molecular mechanism of antioxidant damage of Achyranthes bidentata and Radix Paeoniae Alba is the main objective of study. Rats were treated with Achyranthes bidentata and Radix Paeoniae Alba. The total protein, nuclear protein and total ribonucleic acid were extracted. The protein levels and messenger ribonucleic acid levels were detected by western blot and quantitative polymerase chain reaction, respectively. The apoptosis of cells was detected and the cell viability and clone formation experiments were carried out. The serum malondialdehyde content of the Achyranthes bidentata and white peony group was lower than that of the control group, while the superoxide dismutase activity was higher than that of the control group, which was statistically significant (p<0.05). The level of nuclear factor erythroid 2-related factor 2 protein in the nucleus increased after treatment with medicated serum. The protein levels and the messenger ribonucleic acid levels of heme oxygenase 1 and superoxide dismutase increased significantly (p<0.05). The percentage of apoptosis, increased cell viability and number of clones treated with medicated serum were significantly higher than those treated with serum, indicating that the compatibility of Achyranthes bidentata and white peony can promote the survival of cells under oxidative stress. Under the joint action of protein kinase C delta and protein kinase, Achyranthes bidentata and Radix Paeoniae Alba up-regulate the expression of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a cancer with a high incidence and mortality of female, threatening women's physical and mental health. Achyranthes bidentata Blume, a traditional Chinese medicine, has been popular in folk due to its effective pharmacology activities including anti-inflammatory and anti-tumour effects. In order to identify the active ingredients from the roots of A. bidentata for treating breast cancer, the separation guided by network pharmacology analysis was employed which led to the isolation of 7 triterpenoids and 10 phytosterones. According to the in vitro experiments, the isolated compounds showed significant inhibitory activities on MCF-7 cells as well as anti-inflammatory activities by attenuating the production of NO and TNF-α in LPS-induced macrophage cells. In conclusion, this study successfully predicted and confirmed the positive impact of triterpenoids and phytosterones on breast cancer, which provided a foundation for further in vivo studies. [ABSTRACT FROM AUTHOR]

Achyranthes bidentata Blume, a traditional Chinese medicine, is widely acknowledged for its function of invigorating the liver and kidneys and as a stranguria-relieving diuretic and used in the treatment of edema, gonorrhea, and other diseases. Polysaccharide (ABPS), isolated from Achyranthes bidentata Blume, has been demonstrated to have multiple biological activities including immunomodulatory effects. However, the mechanisms underlying the effects of ABPS have not been fully investigated. The present study is conducted to explore the underlying mechanism of immunomodulatory activities of ABPS. Results showed that ABPS significantly increased the secretion of IL-1β and TNF-α in J744 A.1 cells. Nitric oxide (NO) also significantly increased after ABPS treatment. The special antibodies (Toll-like receptor 4 (TLR4) antibody and CD14/TLR4 antibody) significantly decreased the activation, while the Toll-like receptor 2 (TLR2) antibody could not abolish this activation. Meanwhile, pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of NF-κB, remarkably inhibited the secretion of IL-1β and TNF-α induced by ABPS in J744 A.1 cells. Western blotting (WB) and confocal laser scanning microscopy (CLSM) showed that ABPS promoted NF-κB translocation into the nucleus. Furthermore, the mRNA and protein expression of TLR4 and MyD88 were significantly increased after ABPS treatment. Taken together, these findings suggested that the immunomodulatory mechanism of ABPS was associated with the secretion of cytokines by stimulating the NF-κB pathway through TLR4/MyD88 signaling. [ABSTRACT FROM AUTHOR]

Achyranthes bidentata Blume, a traditional Chinese medicine, is widely acknowledged for its function of invigorating the liver and kidneys and as a stranguria-relieving diuretic and used in the treatment of edema, gonorrhea, and other diseases. Polysaccharide (ABPS), isolated from Achyranthes bidentata Blume, has been demonstrated to have multiple biological activities including immunomodulatory effects. However, the mechanisms underlying the effects of ABPS have not been fully investigated. The present study is conducted to explore the underlying mechanism of immunomodulatory activities of ABPS. Results showed that ABPS significantly increased the secretion of IL-1β and TNF-α in J744 A.1 cells. Nitric oxide (NO) also significantly increased after ABPS treatment. The special antibodies (Toll-like receptor 4 (TLR4) antibody and CD14/TLR4 antibody) significantly decreased the activation, while the Toll-like receptor 2 (TLR2) antibody could not abolish this activation. Meanwhile, pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of NF-κB, remarkably inhibited the secretion of IL-1β and TNF-α induced by ABPS in J744 A.1 cells. Western blotting (WB) and confocal laser scanning microscopy (CLSM) showed that ABPS promoted NF-κB translocation into the nucleus. Furthermore, the mRNA and protein expression of TLR4 and MyD88 were significantly increased after ABPS treatment. Taken together, these findings suggested that the immunomodulatory mechanism of ABPS was associated with the secretion of cytokines by stimulating the NF-κB pathway through TLR4/MyD88 signaling.

BACKGROUND: Achyranthes bidentata can inhibit extracellular matrix degradation of the cartilage and promote the repair of articular chondrocytes. Exosomes widely exist in the synovial fluid of the knee joint and carry a large number of cytokines to play specific biological functions and regulate matrix metalloproteinase. Achyranthes bidentata is speculated to play a role in the treatment of knee osteoarthritis through exosomes OBJECTIVE: To investigate whether Achyranthes bidentata alcohol extract can regulate exosomes of synovial fibroblasts to inhibit extracellular matrix degradation of the cartilage. METHODS: Synovial fibroblasts were cultured and treated with PBS, 100 mg/L Achyranthes bidentata alcohol extract or 10 mmol/L glucosamine. Exosomes were extracted from the cell supernatant, and labeled as EXOs-PBS, EXOs-Achyranthes bidentata, and EXOs-glucosamine. Rabbit models of knee osteoarthritis were constructed, and EXOs-PBS (blank control group), EXOs-Achyranthes bidentata (experimental group), and EXOs-glucosamine (positive control group) were injected into the articular cavity of the rabbit models, respectively, once a week for 5 consecutive weeks. The joint mobility was measured before and after treatment. Degree of improvement of joint adhesion was calculated. Synovial fluid of the knee joint was extracted to detect matrix metalloproteinases 1, 3, and 9 using enzyme-linked immunosorbent assay. Articular cartilage matrix was extracted to detect cartilage matrix glycosaminoglycan content using DMB staining kit. RESULTS AND CONCLUSION: The exosomes of synovial fibroblasts were successfully extracted, and the improvement of joint adhesion in the experimental group was (74.60±8.05)%, which was significantly higher than that in the blank control group [(54.00 ±6.96)%, P < 0.05). The levels of matrix metalloproteinases 1 and 3 in the knee joint fluid of model rabbits in the experimental group were significantly lower than those in the blank control group (P < 0.05). The content of glycosaminoglycan in articular cartilage matrix of model rabbits in the experimental group was (330.83±26.71) mg/L, which was significantly higher than that in the blank control group [(258.21±41.76) mg/L, P < 0.05). The above results of the experimental group were basically the same as those of the positive control group (P > 0.05). Achyranthes bidentata alcohol extract can treat exosomes of synovial fibroblasts, alleviate knee joint mobility of knee osteoarthritis rabbits, reduce the levels of matrix metalloproteinases 1 and 3 in synovial fluid of the knee joint, inhibit the degradation of extracellular matrix and protect the articular cartilage. [ABSTRACT FROM AUTHOR]

The root of Achyranthes bidentata Blume (AB) is a well-known traditional Chinese medicine for treating osteoporosis. Plenty of studies focused on the pharmacological mechanism of the whole extract; however, the contribution of different components to the anti-osteoporosis effect remains unknown. The aim of this study is to explore the anti-osteoporosis mechanism of different components of crude and salt-processed AB under the guidance of network pharmacology, metabolomics, and microbiomics. First, network pharmacology analysis was applied to constructing the compound-target-disease network of AB to provide a holistic view. Second, the anti-osteoporosis effects of the four components were evaluated in female Wistar rats. The subjects were divided into a normal group, a model group, a 17α-estradiol (E2)-treated group, a polysaccharide-component-treated groups, and a polysaccharide-knockout-component-treated groups. All the serum, urine, and feces samples of the six groups were collected after 16 weeks of treatment. Biochemical and microcomputed tomography (μCT) parameters were also acquired. Coupled with orthogonal partial least-squares discrimination analysis, one dimensional nuclear magnetic resonance (NMR) was used to monitor serum metabolic alterations. A total of twenty-two biomarkers, including lipids, amino acids, polyunsaturated fatty acids, glucose, and so on were identified for the different components-treated groups. Through pathway analysis, it is indicated that glyoxylate and dicarboxylate metabolism, glycine, serine, and threonine metabolism, alanine, aspartate, and glutamate metabolism, d-glutamine, and d-glutamate metabolism were the major intervened pathways. Levels of these biomarkers shifted away from the model group and were restored to normal after treatment with the four components. In addition, 16S rDNA sequencing demonstrated that the abundance of Anaerofilum, Rothia, and Turicibacter bacteria was positively correlated with an anti-osteoporosis effect, whereas the abundance of Oscillospira was negatively correlated. The osteoprotective effect of the polysaccharide components of crude and salt-processed AB is related to the regulation of the abundance of these gut microbiota.

Achyranthes bidentata and Achyranthes aspera are saponin and steroid rich medicinal plants, used extensively for therapeutic treatments in Traditional Chinese Medicine (TCM) and Ayurveda. A. bidentata is reported to be one of the rare and extensively exploited medicinal plant species that face the issue of being endangered. Finding qualitative substitute with identical phyto-constituents contributing to similar composition and pharmacological benefits will help in reducing the burden of exploitation of the natural habitats of such plants. In the present study, a comparative metabolite analysis of the whole drug and specific tissues isolated by laser micro-dissection (LMD) was carried out for both the selected species, by use of ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). The results of the study indicate that the cortex and the medullary ray tissues are rich in their content of steroidal and saponin constituents such as (25S)-inokosterone-20,22-acetonide, ginsenoside Ro, bidentatoside II and achyranthoside B. Metabolite profiling of the whole tissues of both the species indicates presence of identical constituents. Thus, it is inferred that A. bidentata and A. aspera can be used as qualitative substitutes for each other.

In this study, effects of soy isoflavones (SIF) on the growth and development, physiology, content of medicinal ingredients and expression levels of enzyme-encoding genes in Achyranthes bidentata Blume under UV-B radiation were systematically investigated. The results showed that UV-B radiation adversely affected the growth and development of A. bidentata seedlings, causing ROS accumulation and the anti-oxidation system to be damaged. However, 1 mg/L exogenous SIF treatment conferred enhanced tolerance under UV-B radiation stress in A. bidentata seedlings by decreasing the concentration of MDA, H2O2, and modulating SOD and POD activities. Furthermore, 1 mg/L SIF reduced the content of oleanolic acid and ecdysterone in leaves and increased the content of oleanolic acid in roots, but had no significant effect on the content of ecdysterone in roots under UV-B radiation stress. SIF had a different degree of influence on the expression levels of antioxidant enzyme genes as well as medicinal ingredients enzyme-encoding genes in A. bidentata. The results showed that 1 mg/L exogenous SIF treatment had a positive effect on the growth, development and physiology in A. bidentata seedlings under UV-B radiation stress. To our knowledge, for the first time we are reporting that the use of 1 mg/L exogenous SIF enhances A. bidentata seedlings tolerance to UV-B radiation stress. [ABSTRACT FROM AUTHOR]

LC–MS analyses of saponin fractions of Achyranthes roots in the Japanese market revealed that there were three patterns for the saponin fraction of their water extracts, i.e., the saponins with a sugar moiety at position 28 [achyranthosides B (3), C (4) and D (5)] were the major constituents, the saponins without sugar moiety at position 28 [betavulgarosides II (10) and IV (11)] were the major constituents, and mixtures of these saponins. In a decoction prepared from the sample which contained 10 and 11 as the major saponins, their amounts were largely decreased compared with those of the water extract. As large amounts of these saponins were found in the precipitates formed by heating of the water extract, these saponins were seemed to precipitate out under heating. When hot water was used for the extraction, 3, 4 and 5 were detected even from the samples whose water extract did not contain these saponins. This was attributed to inhibition of endogenous esterase which hydrolyzes the ester linkage at position 28. When saponins were extracted with reagent grade 1-butanol, in addition to the decrease of the amounts of highly polar saponins, oxidative decarboxylation of 3 and 10 occurred resulting in formation of achyranthoside E (6) and spinacoside D (12), respectively. As these changes were not observed with HPLC grade 1-butanol, which contain not more than 5 ppm of peroxide impurities, the change was attributable to the peroxide impurities contained in the reagent grade 1-butanol. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have shown that synovial fluid cytokines are important factors responsible for knee pain. Achyranthes bidentata can promote the repair of knee chondrocytes, relieve inflammation of the knee joint, and ease knee pain. Whether Achyranthes bidentata can regulate the level of cytokines in the synovial fluid of knee osteoarthritis is still unclear. OBJECTIVE: To investigate the effect of total saponins of Achyranthes bidentata on cytokine profiles of synovial fluid in experimental rabbits with knee osteoarthritis. METHODS: Eight New Zealand rabbits were randomized into experimental and control groups (n=4/group). A rabbit model of knee osteoarthritis was established. At 2 days after modeling, the total saponins of Achyranthes bidentata and distilled water were administered in the experimental and control group, respectively. Range of motion of the knee joint was measured after 2 weeks of administration. The synovial fluid of the knee joint was extracted from each rabbit. The levels of inflammatory cytokines and chemokines were measured by Luminex. The levels of matrix metalloproteinases 1, 2, 3 mRNA were measured by ELISA. The study protocol was approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine (approval No. 2018-31). RESULTS AND CONCLUSION: The range of motion of the knee joint in the experimental group was significantly higher than that in the control group (P < 0.05). Compared with the control group, the expression levels of inflammatory factors interleukin 1α, interleukin 1β, interleukin 10, tumor necrosis factor α, chemokines CCL3, CXCL8, CXCL9, matrix metalloproteinases 1, 2, 3 decreased significantly after treatment (P < 0.05). These findings indicate that Achyranthes bidentata total saponins can alleviate knee dysfunction in knee osteoarthritis rabbits, and reduce the level of cytokines in the synovial fluid of the knee joint, thus reducing inflammation and protecting the cartilage. [ABSTRACT FROM AUTHOR]

Achyranthes bidentata has been traditionally used in China as a nature remedy for osteoporosis; however, little is known about the osteoprotective effects of its polysaccharides. The crude A. bidentata polysaccharide (AB70) was prepared by hot water extraction- ethanol precipitation method and a homogeneous fructan (ABW70-1) was purified from AB70 by ion-exchange and gel filtration column chromatography. Structural analysis indicated that ABW70-1 was composed of (2 → 1)-linked- β - d -fructofuranosyl (Fru f), (2 → 6)-linked- β - d -Fru f and (2 → 1,6)-linked- β - d -Fru f residues, and terminated with fructose and glucose residue. AB70 treatment for 13 weeks has shown a therapeutic effect on ovariectomized rats by restoring bone mineral content and biomechanical properties of the femur. Moreover, such osteoprotective effects of AB70 on bone mass were accompanied by improving trabecular bone microarchitecture and decreasing serum levels of bone turnover biomarkers. Furthermore, ABW70-1 stimulated the osteogenic differentiation of MC3T3-E1 cells by promoting cell proliferation, ALP activity, mineral nodules formation and the gene expression of Osx , Ocn and Bsp. These results suggest that A. bidentata polysaccharides have a great potential in the prevention and treatment of osteoporosis. Unlabelled Image • Water soluble crude polysaccharide (AB70) was extracted from Achyranthes bidentata. • AB70 improved bone mineral content and biomechanical properties in OVX rats. • A homogeneous fructan, ABW70-1, was purified from AB70. • ABW70-1 stimulated osteogenic differentiation of MC3T3-E1 cells. • ABW70-1 upregulated gene expression of Osx , Ocn and Bsp. [ABSTRACT FROM AUTHOR]

Achyranthes bidentata is a popular Chinese medicine, that has its place in the treatment of spasm, osteodynia of the lumbar region and knees. The complete chloroplast (cp) genome of A. bidentata was determined. The complete cp genome is 151,543 bp in length and includes a large single-copy (LSC) region of 83,922 bp, a small single-copy (SSC) region of 17,251 bp, and a pair of inverted repeat regions (IRs) of 25,185 bp. It encodes 131 genes, including 86 protein-coding genes, eight rRNAs, and 37 tRNAs. Phylogenetic analysis indicates that four samples of A. bidentata formed a clade with a 100% bootstrap value.

Achyranthes bidentata (Amarathaceae) has been commonly used as a traditional Chinese medicine in the treatment of osteoporosis and bone nonunion. Here, the complete chloroplast genome of A. bidentata was assembled and characterized. The cp genome is 151,451 bp in length, composed of a pair of 25,150 bp inverted repeat (IR) regions separated by a large single-copy (LSC) region of 83,899 bp and a small single-copy (SSC) region of 17,252 bp. The whole cp genome of A. bidentata contains 130 genes(85 protein-coding genes, 37 tRNAs and eight rRNAs) and the overall GC content is 36.5%. Phylogenetic analysis based on the cp genome data showed that A. bidentata was close to Cyathula capitata.

Background: Osteoporosis is a prevalent bone metabolism disease characterized by a reduction in bone density, leading to several complications that significantly affect patients' quality of life. The Achyranthes bidentata-Dipsacus asper (AB-DA) herb pair is commonly used in Traditional Chinese Medicine (TCM) to treat osteoporosis. This study aimed to investigate the therapeutic compounds and potential mechanisms of AB-DA using network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. Methods: Identified compounds of AB-DA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), TCM@Taiwan Database, BATMAN-TCM, and relevant literature. The main bioactive ingredients were screened based on the criteria of "OB (oral bioavailability) ≥ 30, DL (drug-likeness) ≥ 0.18." Potential targets were predicted using the PharmMapper and SwissTargetPrediction websites, while disease (osteoporosis)-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The PPI network and KEGG/GO enrichment analysis were utilized for core targets and pathway screening in the STRING and Metascape databases, respectively. A drug-compound-target-pathway-disease network was constructed using Cytoscape software to display core regulatory mechanisms. Molecular docking and dynamics simulation techniques explored the binding reliability and stability between core compounds and targets. In vitro and in vivo validation experiments were utilized to explore the anti-osteoporosis efficiency and mechanism of sitogluside. Results: A total of 31 compounds with 83 potential targets for AB-DA against osteoporosis were obtained. The PPI analysis revealed several hub targets, including AKT1, CASP3, EGFR, IGF1, MAPK1, MAPK8, and MAPK14. GO/KEGG analysis indicated that the MAPK cascade (ERK/JNK/p38) is the main pathway involved in treating osteoporosis. The D-C-T-P-T network demonstrated therapeutic compounds that mainly consisted of iridoids, steroids, and flavonoids, such as sitogluside, loganic acid, and β-ecdysterone. Molecular docking and dynamics simulation analyses confirmed strong binding affinity and stability between core compounds and targets. Additionally, the validation experiments showed preliminary evidence of antiosteoporosis effects. Conclusion: This study identified iridoids, steroids, and flavonoids as the main therapeutic compounds of AB-DA in treating osteoporosis. The underlying mechanisms may involve targeting core MAPK cascade (ERK/JNK/p38) targets, such as MAPK1, MAPK8, and MAPK14. In vivo experiments preliminarily validated the anti-osteoporosis effect of sitogluside. Further in-depth experimental studies are required to validate the therapeutic value of AB-DA for treating osteoporosis in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Li, Guo, Tan, Xiang and Ouyang.)

Achyranthes bidentata is a herbal plant commonly used in the treatment of osteoporosis and bone nonunion with traditional Chinese medicine. Achyranthes bidentata alcohol is a major component extracted from Achyranthes bidentata, which has been proved to be able to exert a variety of pharmacological effects, such as anti-inflammation, antipyresis, anti-rheumatism, diuresis and anti-osteoporosis. Thirty male Sprague-Dawley rats aged 4 weeks were used in the experiment. All primary rat osteoblasts were cultured and amplified for further experiments. The osteoblasts were divided into six groups (5 rats in each group): the culture medium control group, the 25 µg/ml achyranthol group, the 50 µg/ml achyranthol group, the 100 µg/ml achyranthol group, 200 µg/ml achyranthol group, and the 25 µM PD98059+200 µg/ml achyranthol group. In this study, the effect of Achyranthes bidentata alcohol on the proliferation of osteoblasts was detected via methyl thiazolyl tetrazolium (MTT) assay. The effect of Achyranthes bidentata alcohol on the alkaline phosphatase (ALP) activity in osteoblasts was analyzed via ALP assay. The effect of Achyranthes bidentata alcohol on the expression of osteoblast marker gene, Runt-related transcription factor 2 (Runx2), was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Moreover, the phosphorylation or activation of extracellular signal-regulated kinase (ERK) in osteoblasts induced by Achyranthes bidentata alcohol was analyzed using western blotting. Achyranthes bidentata alcohol increased cell proliferation in a dose-dependent manner, increased the micro ribonucleic acid (miRNA) level in Runx2, enhanced the ALP activity in osteoblasts, and stimulated the activation of ERK (P<0.05). The expression of Runx2 with the inhibitor PD98059 was decreased significantly compared with that in the Achyranthes bidentata alcohol group (P<0.01). Immunohistochemical results manifested that the percentage of Runx2 positive cells in treated tissues was obviously higher than that in untreated tissues (P<0.01). Therefore, Achyranthes bidentata alcohol promotes the proliferation capacity of osteoblasts in a dose-dependent manner, enhances the expression of miRNA in Runx2, and stimulates the osteogenic differentiation of osteoblasts through activating the ERK signal transduction pathway. [ABSTRACT FROM AUTHOR]

The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aβ 1–40-induced Alzheimer's disease (AD) model in rats. ABS only contained 135.11 ± 4.28 mg of ecdysterone per gram. ABS (50 mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aβ 1–40 in rats. ABS (50 mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aβ 1–40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aβ 1–40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aβ 1–40. ABS alone (50 mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aβ 1–40-induced AD rat model. [ABSTRACT FROM AUTHOR]

Ultraviolet-B radiation (UV-B) can boost the accumulation of terpenoids in plants. Here, Ach-yranthes bidentata Blume plantlets were exposed to UV-B radiation for different durations (1, 2, 3 and 4 h) to understand its effect on the accumulation of the medicinally important secondary metabolites oleanolic acid and ecdysterone. Our results showed that UV-B radiation led to reduced chlorophyll a, chlorophyll b and carotenoid production. Additionally, enzymatic antioxidants accumulated in the plant to detoxify ROS under UV-B radiation. Nine known enzyme-encoding genes (HMGS, HMGR, PMK, FPS, SS, SE, GGPPS, β-AS and CAS) involved in secondary metabolism in A. bidentata were analyzed at the transcriptional levels post-UV-B treatment from 0 to 4 h. RT-qPCR analysis revealed an upregulation in the HMGS, HMGR, PMK, FPS, SS, SE, β-AS and CAS genes that are related to the production of oleanolic acid and ecdysterone. We observed a significant increase in oleanolic acid and ecdysterone content at 3 and 2 h UV-B radiation exposure, respectively. The present work provides evidence that UV-B radiation in mild doses can enhance the concentration of these secondary metabolites by upregulating the relative expression levels of key enzyme genes involved in oleanolic acid and ecdysterone biosynthesis. This study provides evidence that short-term UV-B treatments can increase A. bidentata secondary metabolite content and may be a safe approach for generating high oleanolic acid and ecdysterone producing plantlets. [ABSTRACT FROM AUTHOR]

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23–1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23–1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC–MS, partial acid hydrolysis and NMR results indicated the backbone of A23–1 was composed of 1, 2, 4-Rha p and 1, 4-Gla p A, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23–1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23–1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23–1. These findings suggested A23–1 was possible one of food sources of human gut Bacteroides spp. • The structure of a pectic polysaccharide A23–1 from A. bidentata was elucidated. • A23–1 could be degraded by human gut Bacteroides spp. • The degradation process might be dictated by three PULs. • There was possible no cross feeding between Bacteroides ovatus and probiotics. • Bacteroides spp. produced SCFAs by utilizing A23–1. [ABSTRACT FROM AUTHOR]

The roots of Achyranthes bidentata Blume are one of the regularly used herbal drugs in Chinese medicine, and has been applied for strengthening the muscle and bone for a long time. However, its effect on muscle remains unclear. This paper aims to explore the anti-muscle atrophy effect of A. bidentata , and to clarify the possible signaling pathways involved. The saponin extract of the roots of A. bidentata (ABSE) was prepared and analyzed, and its activity on myoblast differentiation was assayed with C2C12 cell culture. ABSE was then orally administered at dosage of 35, 70 and 140 mg/kg/day to disuse-induced muscle atrophy mice. The studies on mice body weight and muscle quality were conducted, and Western blot was used for exploring the possible signaling pathways involved in the muscle protective action aided with transcriptome analysis. The total saponin content of ABSE was 59.1%. ABSE promoted the C2C12 cells differentiation to myotube in C2C12 differentiation assay. Further study with disuse-induced muscle atrophy mice model demonstrated that ABSE significantly increased muscle fiber diameter as well as the proportion of slow muscle fibers. Possible mechanism study aided with transcriptome analysis revealed that ABSE alleviated muscle atrophy at least through activation of PI3K/Akt pathway in vivo & vitro. The saponin extract of the root of A. bidentata (ABSE) has a protective effect on muscle atrophy, and showed a considerable potential in prevention and treatment of muscle atrophy. [Display omitted] • The saponin extract of A. bidentata (ABSE) was prepared and analyzed. • ABSE promoted the differentiation of C2C12 cells to myotubes. • ABSE displayed a protective effect on muscle atrophy in vivo. • ABSE activated PI3K/Akt pathway in vivo & in vitro. • ABSE increased protein levels of Myogenin and MyoD. [ABSTRACT FROM AUTHOR]

The osteoinductive effect of crude and salt-processed Achyranthes bidentata is associated with the serum metabolites. Grey relationship analysis between the serum metabolites and osteoinductive effect will help to clarify the bioactive serum metabolites. First, an ultra-high performance liquid chromatography time-of-flight mass spectrometry method was used to develop serum metabolic fingerprint of rats after oral administration of crude and salt-processed Achyranthes bidentata. The MS1 and MS2 data of serum metabolites were scanned in the range of m/z 100–1500 and 50–1200, respectively. The chemical structures of the metabolites were thoroughly elucidated. Two prototypes and twelve metabolites have been identified. Second, osteoblasts were cultured with the drug-containing serum at different time points. The osteoinductive effect of crude and salt-processed Achyranthes bidentata was evaluated by detecting the proliferation rate and alkaline phosphatase activity of osteoblasts. Third, grey correlation analysis was utilized to elucidate the spectral-effect relationship between serum metabolic fingerprints and osteoinductive effect. Finally, the correlation coefficients of ten metabolites, i.e., oleanolic acid, poststerone-M1, chikusetsusaponin V-M1, oleanolic acid-M2, oleanolic acid-M4, spinacoside D-M1, chikusetsusaponin I-M1, betavulgaroside IV-M2, chikusetsusaponin IVa and achyranthoside IV-M1 were above 0.7. Collectively, our work will provide helpful knowledge for the future research on Achyranthes bidentata. • Serum metabolic fingerprint of rats receiving Achyranthes bidentate was developed. • The osteoinductive effect of crude and salt-processed Achyranthes bidentata was evaluated. • Grey correlation analysis was utilized to elucidate the spectral-effect relationship. [ABSTRACT FROM AUTHOR]

Osteoporosis is a frequent disease among the elderly especially in postmenopausal women. Achyranthes bidentata is a traditional Chinese medicine used to strengthen bones. Here, A. bidentata polysaccharides (ABPs) were confirmed to have anti-osteoporosis effects. This study discovered biomarkers by comparing normal and osteoporosis rats and evaluated the effects of ABPs on osteoporosis based on the UPLC/Q-TOF-MS-based metabolomics analysis. We could then predict the underlying mechanisms from the perspective of metabolomics. Osteoporotic rats were treated with ABPs, and serum was then sampled for metabolic analysis. Glutarylcarnitine, lysoPC (18:1) and 9-cis-retinoic acid were identified as biomarkers. The ABPs could significantly increase these biomarkers, and this indicated that ABPs curing osteoporosis regulated lipid metabolism. The UPLC/Q-TOF-MS-based metabolomics analysis offered a potential strategy to evaluate the anti-osteoporosis effects of ABPs and to explain the relative mechanisms. Furthermore, the ABPs have good potential for treating osteoporosis. [ABSTRACT FROM AUTHOR]

With the continuous progress of traditional Chinese medicine extraction technology in recent years, the active components of traditional Chinese medicine have been continuously extracted and analyzed. In this paper, the authors studied the effect of aerobic exercise combined with the extract of the Achyranthes bidentata on the serum indexes of T2DM rats. Through systematic analysis of measurement indexes of Chinese medicine treatment group, we found that all indexes of FPG, INS, NOXs, ROS and SOD all showed a marked improvement, which fully proved the effect of Achyranthes bidentata extract on improving the condition of rats with type 2 diabetes mellitus. In this experiment, we can see that aerobic exercise can relieve diabetic patients' condition by comparing and analyzing various indexes of type II diabetes in experimental rats. At the same time, the effect of the combination of aerobic exercise and the extract of Achyranthes bidentata is obviously better than that of the extract of pure Achyranthes bidentata. [ABSTRACT FROM AUTHOR]

A simple, accurate and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry approach was established for the simultaneous determination of β -ecdysterone, 25 S -inokosterone, ginsenoside Ro, chikusetsusaponin IV and chikusetsusaponin IVa in rat plasma after oral administration of raw and salt-processed Achyranthes bidentata extract. The saponins were completely separated on a Waters BEH C 18 UHPLC column by using acetonitrile/0.1% formic acid-water as mobile phases. The mass analysis was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with negative scan mode. The sample preparations for protein removal were accomplished using a simple acetonitrile precipitation method. The calibration curves displayed good linearity (r 2  > 0.9998) with the concentration ranges of 24.4–6100 ng mL −1 , 25.6–6400 ng mL −1 , 20.4–8500 ng mL −1 , 21.6–5400 ng mL −1 , 21.6–6100 ng mL −1 for the five saponins, respectively. The intra-day and inter-day precisions (RSD) of the five saponins were less than 3.95% and the bias of the accuracies ranged from −4.50% to 4.84%. The extraction recoveries of the five saponins ranged from 95.2% to 104.8% and the matrix effects were satisfactory. In comparison with the raw group, the parameters of C max and AUC 0-t of β -ecdysterone, 25 S -inokosterone, ginsenoside Ro, and chikusetsusaponin IVa elevated remarkably ( p <   0.05 ) after oral delivery of the extract of salt-processed Achyranthes bidentata , which revealed that salt-processing could increase bioavailability of β -ecdysterone, 25 S -inokosterone, ginsenoside Ro and chikusetsusaponin IVa. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Achyranthes L. (Amaranthaceae), also known as Chaff Flower and Niuxi/牛膝, mainly includes two famous medicinal species namely A. bidentata and A. aspera. A. bidentata has been widely used as blood-activating and stasis-resolving medicine for the treatment of various diseases including amenorrhea, dysmenorrhea, lumbago, gonalgia, paraplegia, edema, stranguria, headache, dizziness, odontalgia, oral ulcer, hematemesis, and epistaxis. A. aspera has been widely used to treat various diseases, including gynecological disorder, asthma, ophthalmia, odontalgia, haemorrhoids, and abdominal tumor, and has been applied to difficult labour, wound healing, insect and snake bites. Aim of this review This review aims to provide systematically reorganized information on distributions, botanical characteristics, ethnopharmacology, chemical constituents, qualitative and quantitative analysis, pharmacological activities, and toxicity of Achyranthes species to support their therapeutic potential. Materials and methods The relevant information on Achyranthes species was gathered from worldwide accepted scientific databases via electronic search (Google Scholar, Web of Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, SciFinder, CNKI). Information was also obtained from International Plant Names Index, Chinese Pharmacopoeia, Chinese herbal classic books, PhD and MSc dissertations, etc. Results A comprehensive analysis of literatures obtained through the above- mentioned sources confirms that the ethnomedicinal uses of Achyranthes species are mainly recorded in China, India, Korea, Pakistan, Ethiopia, Kenya, Sri Lanka, Bangladesh, Philippines, etc. Phytochemical investigations revealed that the major bioactive substances of Achyranthes plants are polysaccharides, polypeptides, triterpenoid saponins, and ketosteroids. Achyranthes plants have been shown to not only act on immune system, nervous system, bone metabolism, and reproduction, but also possess a wide range of biological activities, including blood-activating, anti-tumor, anti-inflammation, anti-arthritis, anti-oxidation, anti-aging, wound healing, etc. Toxicity studies indicated that A. bidentata and A. aspera seem non-toxic at the common therapeutic doses. Conclusions A. bidentata and A. aspera are very promising to be fully utilized in the development of nutraceutical and pharmaceutical products. There are, however, needs for further in-depth studies to confirm some ethnomedicinal uses of Achyranthe s plants and to elucidate the scientific connotation of the widely documented property of conducting drug downward of A. bidentata . In addition, other widespread Achyranthes species like A. japonica and A. rubrofusca ought to be studied. Likewise, systematic comparative studies of the chemical constituents of medicinal Achyranthes plants resources with the same local name are also needed. Furthermore, not only should the investigations on the structure-activity relationship of the main bioactive compounds triterpenoid saponins and ketosteroids be carried out, but the pathways of absorption, distribution, metabolism, and excretion ought to be clarified. Last but not least, there is also a need to evaluate the long-term chronic toxicity and acute toxicity in vivo of the main bioactive compounds. [ABSTRACT FROM AUTHOR]

Previous phylogeographic studies of the warm-temperate zone in China focused on woody plants, but little attention was given to the climate-sensitive herbaceous plants. In this work, we implemented a phylogeographic survey on the perennial herb Achyranthes bidentata in China's warm-temperate zone. The sequence variation of cpDNA and nDNA was examined across 209 individuals from 21 populations. A total of 11 chlorotypes and 26 ribotypes were identified. The cpDNA data showed weak population genetic differentiation and could not divide the 21 populations into different genetic groups. By contrast, the nDNA data revealed stronger genetic differentiation than cpDNA and could divide these populations into two genetic groups. The cpDNA and nDNA data both gave unambiguous signs of recent sudden population expansion. Based on the cpDNA and nDNA data, the estimated time of population expansion occurred at interglacial Marine Isotope Stage (MIS) 9 of the Penultimate Glaciation in China. The cpDNA and nDNA data suggested that the glaciation during this period deeply influenced the current distribution patterns and intraspecific divergence of A. bidentata. Our survey showed that A. bidentata tracked climatic oscillations by a large range of southward retreat into three main refugia during MIS 8, followed by the sudden northward expansion from these refugia during MIS 9. [ABSTRACT FROM AUTHOR]

Identifying genetic diversity patterns is fundamentally important for effective species management and conservation. In this study, we used five microsatellite loci to investigate the genetic diversity and population differentiation of Achyranthes bidentata in Dao Di and its surrounding region. Our analysis of microsatellite data indicated the level of genetic diversity of A. bidentata ( H T = 0.333) was lower than other plants. The results showed no significant genetic diversity differences and population genetic differentiation between the Dao Di and surrounding region. Significant temperature differences (Bio2: mean diurnal range and Bio7: temperature annual range) were found between the Dao Di and surrounding region, which may improve the accumulation of medicinal ingredients of populations in the Dao Di. The populations of A. bidentata were divided into two genetic groups, which was caused by five temperature variables (Bio1, Bio4, Bio7, Bio9, and Bio11). This study thus provides an important case for over-collecting within limited ranges in affecting population diversity and bioclimate variables for different producing area in driving population differentiation. [ABSTRACT FROM AUTHOR]

A novel technology coupling extraction and foam fractionation was developed for separating the total saponins fromAchyranthes bidentata. In the developed technology, the powder ofA. bidentatawas loaded in a nylon filter cloth pocket with bore diameter of 180 µm. The pocket was fixed in the bulk liquid phase for continuously releasing saponins. Under the optimal conditions, the concentration and the extraction rate of the total saponins in the foamate by the developed technology were 73.5% and 416.2% higher than those by the traditional technology, respectively. The foamates obtained by the traditional technology and the developed technology were analyzed by ultraperformance liquid chromatography–mass spectrometry to determine their ingredients, and the results appeared that the developed technology exhibited a better performance for separating saponins than the traditional technology. The study is expected to develop a novel technology for cost effectively separating plant-derived materials with surface activity. [ABSTRACT FROM PUBLISHER]

The aim of this work was to study the plant regeneration and Agrobacterium-mediated transformation of Achyranthes bidentata using cotton EREBP gene. Results showed that the callus induction rate of stems from A. bidentata was the highest (100%) and bud was in approximately 70% of calli from stems. However bud differentiation rate of the callus from leaves and petioles was very low. Compared with ceftriaxone, 200mg/L cefotaxime could completely control Agrobacterium tumefaciens and had relatively less toxic action on the stems of A. bidentata. In addition, the induction rate of callus resistant to hygromycin was the highest when infected for 3 min and co-cultivated for 3 d. Six positive transgenic plants transformed with pCAMBIA1304-GhEREB2 expression vector were obtained and confirmed by PCR. The expression of target gene GhEREB2 was detected in five transgenic plants by RT-PCR. In brief, an efficient system of genetic transformation and plant regeneration was established for A. bidentata.