The metabolomic profile shows that Echinops latifolius Tausch improves the trabecular microarchitecture of ovariectomized rats mainly through the intervention of amino acid and glycerophospholipid metabolism. (2023)


Osteoporosis is a metabolic bone disease characterized by pathological bone loss, reduced bone strength and microarchitectural deterioration of bone tissue (Alexandre and Vico, 2011; Kerschan-Schindl, 2016; Tsukamoto et al., 2019). There are two categories of osteoporosis, with postmenopausal osteoporosis (PMOP) being the most common primary form (Tarantino et al., 2017). With the acceleration of the aging process in the world, osteoporosis has become a major health problem, especially among middle-aged and elderly women, due to its high prevalence and health costs, which places a great burden on finances. government and health systems (Harvey et al., 2010). The impact of TRHs on bone metabolism, including changes in estrogen levels and improvement in the bone microenvironment, has been documented by many studies (Cranney and Wells, 2003; Gambacciani and Vacca, 2004; MacLennan et al., 1999). However, long-term estrogen supplementation carries several risks, such as cardiovascular disease, ovarian cancer, breast cancer, and endometrial cancer, which are no longer recommended (Komm et al., 2015). Although phytoestrogens have reported fewer side effects (Beck et al., 2005; Woclawek-Potocka et al., 2005), combination drug therapy was a new trend today for the complexity of osteoporosis (Gur et al., 2002; Vescini et al., 2016). Consequently, Chinese Herbal Medicine (CHM) has become a new drug bank for the treatment of complex diseases due to its multi-target properties. Many MCHs have been used in China for centuries to treat perimenopausal syndrome, such as: 2018). ), Echinops latifolius Tausch (Zhao and Xie, 2019), etc.

Echinops latifolius Tausch (ELT), belonging to the Asteraceae family, was mainly distributed in Northeast China, North China and Northwest China, and the inflorescences of this plant were used as medicinal parts in Inner Mongolia, the inflorescences of this plant were often used as medicinal parts, they have been used to fight osteoporosis, strengthen tendons and bones, remove heat from bones, and relieve bone tingling (Committee, 2015). Pharmacological mitigation of ELT in ovariectomy-induced bone loss through regulation of interleukin-1 and alkaline phosphatase levels has been reported in cumulative studies (Gao et al., 2016; Gao and Guan, 2016). In a previous clinical study (Jun and Jinghua, 2019), osteodynia associated with osteoporosis in postmenopausal women can be alleviated by administering an ELT formulation, suggesting that ELT may have an anti-osteoporosis effect. However, the underlying mechanisms of TLE in the treatment of osteoporosis have not been elucidated.

Considering the numerous compounds in CHM, the mechanism of CHM is too complex to be established by conventional experimental methods alone. In this sense, there is an urgent need to develop new and appropriate approaches to deal with this problem. Metabolomics is characterized as sensitive and unbiased, used to comprehensively study changes in metabolite content in biological samples to understand disease mechanisms (Johnson et al., 2016). Recently, metabolomics has been a crucial tool to identify potential disease diagnostic biomarkers, qualify traditional Chinese medicine formulations, and characterize CHM (Yang and Lao, 2019). Many highly sensitive, high-throughput instruments, including liquid chromatography-mass spectrometry (LC-MS) (Zhou et al., 2012), nuclear magnetic resonance (NMR) spectroscopy (Larive et al., 2015), gas chromatography- mass spectrometry (GC-MS)) (Papadimitropoulos et al., 2018), capillary electrophoresis-mass spectrometry (CE-MS) (Ramautar et al., 2019) and multivariate analysis methods such as principal component analysis (PCA ), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) are widely used in metabolomics research. Metabolomics is a "completeness and systematization" analytical method consistent with the "multiple components and multiple targets" theory in CHM. In order to fully understand the mechanisms of action and therapeutic efficacy of herbal medicines, a comparison of the metabolite profile before and after treatment should be analyzed.

In this study, the ovariectomized rat model (OVX), a classic PMOP model (Johnston and Ward, 2015; Kalu, 1991), was chosen to study the pathological features of PMOP. The effects of ELT on trabecular microarchitecture and biochemical markers of OVX mice were studied. An untargeted metabolomics strategy was applied to analyze the metabolic profile of OVX rats, evaluate the anti-osteoporotic efficacy of ELT and understand the mechanism of action of ELT in anti-osteoporosis. At the same time, the most relevant potential biomarkers and signaling pathways related to osteoporosis were revealed through analysis of signaling pathways and construction of correlation networks. To the best of our knowledge, we investigated for the first time the therapeutic mechanism of ELT in osteoporosis using the metabolomics approach, which not only provides modern scientific evidence for the therapeutic effect and mechanism of action of ELT in osteoporosis, but also offers a new perspective on the Modernization. CHM Search.

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chemicals and reagents

Osteocalcin, precollagen type I carboxyl-terminal peptide (PTICP), tartrate-resistant acid phosphatase (TRAP), and deoxypyridinoline (DPD) assay kits were obtained from Hua Lian Institute of Biotechnology (Wuhan, China). Chloral hydrate, saline, was purchased from Ze Sheng Institute of Biotechnology (Hohhot, China). HPLC grade methanol and formic acid were obtained from Fisher Scientific Corporation (Loughborough, UK). Ultra high purity water (18.2 MΩ) was obtained from an ALH-600-U

Echinops latifolius Tausch improved trabecular microarchitecture and biochemical markers in ovariectomized rats

The animal model of postmenopausal osteoporosis established by ovarian excision was successfully performed and verified by monitoring vaginal keratinization. As shown in Fig. 1, rats in the sham group had a general estrous cycle (Fig. 1a,b). In contrast, vaginal cells from OVX mice consisted of leukocytes, which was evidence of constant diestrus (Fig. 1c).

Morphologically, a small, thin, and sparse trabecular region was observed in the tibia of OVX rats compared to the sham group (Fig. 2


OVX induced postmenopausal osteoporosis accompanied by a marked improvement in bone resorption, increased bone fragility, and decreased bone tissue structure, in part due to estrogen loss (Nian et al., 2009). In the present experiment, ELT demonstrated potent anti-osteoporosis activity, evidenced by improvement in trabecular microarchitecture and in the levels of biochemical indicators. Based on the values ​​of histomorphometric parameters, the deterioration of bone health in OVX mice


Osteoporosis, particularly PMOP, has become a global health problem that is seriously affecting women's health. There is an urgent need to develop suitable therapeutic alternatives for PMOP with few side effects. ELT was a new candidate for PMOP therapy according to the previous report. The ELT mechanism in PMOP has yet to be discovered. Pharmacological experiments and an untargeted metabolomics strategy were used to assess the efficacy and mechanism of ELT in OVX mice in this experiment. morphological,

Author Contributions

Jianping Gao and Peifeng Xue conceived and designed the experiments. Jiaqi Wang conducted the experiment and conducted the animal tests. Xin Dong performed the data analysis and wrote the article. Feixiang Ma, Chunyan Li, Ren Bu and Jingkun Lu collected samples of Echinops latifolius Tausch outside. Jiaqi Wang and Xin Dong performed the data interpretation. All authors approved the final manuscript.

Declaration of Competing Interests

The authors declare that there is no conflict of interest in the publication of this article.

expression of gratitude

This work was financially supported byNational Science Foundation of China(81860756,81960758),Inner Mongolia Scientific Foundation(2017MS08122,2019MS08111),Scientific and technological research program at universities in Inner Mongolia Autonomous Region(NJZY19099),Leading Science and Technology Innovation Project in Inner Mongolia(02039001).

  • Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (C. paniculatum), is a traditional medicinal plant widely used by East Asians. The roots and rhizomes of this herb have been called "Xu-Chang-Qing" in China since the Qin or Han Dynasty (221-220 BC). It is naturally hot and spicy and is associated with the Liver and Stomach meridians. The effectiveness of this herb also consists in expelling wind, dissolving dampness, relieving pain and itching. It is used to treat the occurrence of rheumatic arthralgia, stomach pain, toothache, lumbago, soft tissue injuries, rubella and eczema.

    The aim of this article is to provide a systematic review of the botany, traditional uses, phytochemistry and pharmacology of C. paniculatum based on studies over the past two decades.

    A comprehensive search of prior literature was performed on databases such as Web of Science, Pubmed, Sciencedirect, American Chemical Society (ACS), Google Scholar, and China National Knowledge Internet (CNKI). The search was based on botany, traditional uses, phytochemistry and pharmacology of C. paniculatum. The search terms were "Cynanchum paniculatum" and "Radix Cynanchi Paniculati". Additionally, some published books were searched for more information about the herb.

    More than 150 compounds have been isolated and identified from C. paniculatum, including C.21steroids, volatile oils, carbohydrates and phenanthroindolizidine alkaloids. Extensive pharmacological activities of extracts or compounds of C. paniculatum in vivo and in vitro have been confirmed, including anti-inflammatory, antinociceptive, sedative, antiviral, antitumor, neuroprotective, snakebite, immunomodulatory, antiradiative, vasodilator, acaricidal and antiadipogenic activities.

    This article reviewed the botany, traditional uses, phytochemistry and pharmacology of C. paniculatum. This herb has been used as a traditional medicine. It has been reported with numerous chemical ingredients and various pharmacological activities with anti-inflammatory, antitumor, neuroprotective agents, etc. In the future, C. paniculatum needs to be studied further, e.g. B. identify the active principles, clarify the pharmacological mechanisms, discuss quality and safety. .

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    International Journal of Biological Macromolecules, Band 161, 2020, S. 909-916

    EPPS, a novel heteropolysaccharide from the roots of Echinops pungens, was extracted with warm water (70 °C) while being purified by column chromatography on DEAE-cellulose A52 and Sephadex G-100. The total carbohydrate content, specific optical rotation and molecular mass of EPPS were 98.3%, -88.2 and 65.7 kDa, respectively. GLC analysis showed that EPPS was a neutral polysaccharide and contained Gal, Glc, Man, Xyl and Ara in ratios of 0.96:5.23:1.00:2.06:1.04. Multiple chemical and instrumental analysis methods such as methylation, periodate oxidation and Smith degradation, partial acid hydrolysis, GLC-MS, FT-IR and NMR (1Mil13C) were used to elucidate the structure of EPPS and their results showed that its skeleton consists of →6)-β-D-Glcp-(1→- branched residues with O-4 (~38%) through →4 -β -L-Arap-(1→, →4)-β-D-Manp-(1→, →4)-β-D-Xylp-(1→, β-D-Xylp-(1→y α -D -Galp-(1→residues. The DPPH elimination capacity of EPPS was lower than that of ascorbic acid at identical concentrations and its EC50the value was 1.91 mg/ml.

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    Neuropathic pain, which has an incidence between 5 and 8% of the general population, remains a challenge in treatment. Shaoyao Gancao Decoction (SGD) is a classic Chinese formula that has been used for pain relief for thousands of years and is now used for neuropathic pain. However, the effective components of SGD for the treatment of neuropathic pain remain unclear.

    To investigate the effect and potential mechanism of SGD against neuropathic pain and further discover the effective components of SGD in treating neuropathic pain.

    SGD was orally administered to model rats with pain-sustaining neuropathic injuries (SNI) for intervention, in vivo components were determined after SGD administration, behavioral indicators, biochemical and metabolomic parameters were applied to assess efficacy. The correlation between the components and the biomarkers was then analyzed by Pearson's correlation method. To further measure the contribution of the components to the effectiveness, a combination of partial least squares regression (PLSR) and the multi-index integral method was performed, according to the respective degree of contribution of the results, the components with the highest apply degree were found to be effective components.

    SGD showed a significant regulatory effect on neuropathic pain that could increase pain threshold and decrease SP, β-EP, PGE2 and NO levels. With the high resolution of the UPLC-Q-TOF/MS technology, a total of 128 SGD compounds were identified and 44 of them were incorporated into the blood. In addition, 40 serum biomarkers were identified and metabolic pathways constructed after the SGD intervention. Important metabolic pathways including glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol anchor biosynthesis, and arachidonic acid metabolism may be involved in the regulation of neuropathic pain. Metabolomics combined with PLSR and a comprehensive multi-index method were used to discover 5 components including paeonol, DL-arabinose, benzoic acid, hispaglabridin A and paeonylactone C as effective components of SGD in the treatment of neuropathic pain. This strategy was used to explore the active components of SGD and to elucidate its possible analgesic mechanism.

    This study shows that SGD significantly alleviates neuropathic pain and clarifies the effective components of SGD for the treatment of neuropathic pain, the strategy can be applied to other classic formulations as an illustrative case study and helps to improve quality and efficacy.

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    Huang-lian-jie-du (HLJDD) decoction is a traditional Chinese medicine recipe for clearing heat, purifying fire, and detoxifying, which can be used to treat sepsis, stroke, Alzheimer's disease, and gastrointestinal ailments. Our previous studies showed that HLJDD can effectively alleviate acute ulcerative colitis (UC) in mice, and its n-butanol fraction (HLJDD-NBA) is the effective fraction. The aim of this study is to further investigate the mechanism of HLJDD and HLJDD-NBA in alleviating UC in mice from a holistic perspective.

    The BABL/c mouse model of acute ulcerative colitis was induced with drinking water containing sodium sulfate and 3.5% (w/v) dextran. At the same time of modeling, HLJDD and HLJDD-NBA were administered orally for treatment, respectively. During the experiment, the clinical symptoms of the mice were recorded and the physiological and biochemical indices of the mice were recorded after the experiment. Furthermore, the plasma metabolites of the mice in each group were detected and analyzed by ultra-high-performance liquid chromatography, quadrupole time-of-flight mass spectrometry and multivariate statistical analysis methods. The potential target pathway of drug intervention was then assessed by differential analysis of metabolite accumulation. Finally, we use molecular simulation docking technology to further investigate the molecular regulatory mechanism of HLJDD and HLJDD-NBA in possible target pathways.

    HLJDD and HLJDD-NBA intervention can significantly reduce the disease activity index of UC mice, inhibit colon length shortening and pathological damage, and alleviate abnormal changes in physiological and biochemical parameters of UC mice. Furthermore, HLJDD and HLJDD-NBA can significantly inhibit the metabolic dysfunction of UC mice, reversing abnormal changes of 24 metabolites in UC mice, and the arachidonic acid pathway and the glycerophospholipid pathway are the target pathways regulated by them. Further literature review and molecular simulation docking analyzes showed that HLJDD and HLJDD-NBA can inhibit the disruption of arachidonic acid and glycerophospholipid pathways by inhibiting COX 2 protein expression and PLA2, 5-LOX activity.

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    Academic Radiology, Volume 23, Issue 3, 2016, pp. 273-283

    Characterization of bone marrow lipid profile in the calcaneus and femoral neck of healthy women with osteopenia and osteoporosis using 3T magnetic resonance spectroscopy (MRE). The ultimate goal was to identify specific metabolites with the potential ability to discriminate between healthy, osteopenic and osteoporotic individuals.

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    MRS spectra were used to quantify and compare bone marrow fat resonances between the three BMD groups. Differences between groups were tested using Welch's analysis of variance. Several comparisons were made using the Games-Howell correction. Relationships between pairs of variables were assessed using linear correlation analysis. A reproducibility analysis was performed for all lipid MRIs at both sites.

    Reproducibility was satisfactory. At the femoral neck, resonances for methylene (L13), glycerol (L41, L43) and total lipids were significantly lower in healthy subjects than in subjects with osteoporosis. On the other hand, L13/glycerol in the calcaneus differed significantly between osteopenic and osteoporotic individuals, while L13/(unsaturated lipids) differed between healthy and osteopenic groups. However, the reproducibility of the unsaturated lipid and glycerol resonances was far from ideal.

    MRS of bone marrow lipid profiles from peripheral skeletal sites may be a promising tool for screening large populations to identify individuals with or at risk of developing osteoporosis. In addition, it provides information on the metabolic changes that occur in the bone marrow during the development of osteoporosis, which depend on the position of the skeleton.

© 2020 Elsevier B.V. All rights reserved.

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