Evidence-based Complementary and Alternative Medicine
·
2021
·Vol. 2021
·期 1
·2894306
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IF 2.63
Hong Chang,Shujie Lv,Tengteng Yuan,Huan Wu,Lei Wang,Ran Sang,Caiyun Zhang,Weidong Chen
Gushuling (GSL), a well-known hospital preparation composed of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of osteoporosis (OP) for decades due to its remarkable therapeutic effect. However, the chemical constituents of GSL are still unclear so far, which limits the in-depth study of its pharmacodynamic material basis and further restricts its clinical application. In this study, we developed a strategy for qualitative analysis of the chemical constituents of GSL in vitro and in vivo . Based on the results of ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) and the UNIFI informatics platform, the chemical constituents of GSL can be determined quickly and effectively. By comparing the retention time, accurate mass, and fragmentation spectrum of the compounds in GSL, a total of 93 compounds were identified or preliminarily identified, including flavonoids, terpenoids, phenylpropanoids, steroids, etc. Among them, nine compounds have been confirmed by standard substances, namely epimedin A, epimedin B, epimedin C, icariin, ecdysterone, calycosin, calycosin-7-glucoside, ononin, and ginsenoside Ro. Fragment patterns and characteristic ions of representative compounds with different chemical structure types were analyzed. At the same time, 20 prototype compounds and 42 metabolites were detected in rat serum. Oxidation, hydration, reduction, dehydration, glutathione S-conjugation, and acetylcysteine conjugation were the main transformation reactions of GSL in rat serum. In this research, the rapid method to characterize the in vitro and in vivo chemical constituents of GSL can not only be used for the standardization and quality control of GSL but also be helpful for further research on its pharmacodynamic material basis.
研究领域:
中药学
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分析化学
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药理学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 7
·1033
·
IF 2.861
Shuanghong Song,Ziyang Gao,Xujun Lei,Yinbo Niu,Yuan Zhang,Cuiqin Li,Yi Lu,Zhezhi Wang,Peng Shang
Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized rats. However, the beneficial effects of the total flavonoids of Drynariae Rhizoma on osteoporosis caused by microgravity or mechanical inactivity remain unknown. This study assessed the effects of total Drynariae Rhizoma flavonoids (DRTF, Qihuang, Beijing, China, national medicine permit No. Z20030007, number of production: 04080081, content of DRTF ≥80%) against bone loss induced by simulated microgravity. A hindlimb unloading tail-suspended rat model was established to determine the effect of DRTF on bone mineral density (BMD), biomechanical strength and trabecular bone microarchitecture. Twenty-eight male Sprague–Dawley rats were divided into four groups: the baseline, control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with DRTF (HLU–DRTF, 75 mg/kg/day) groups. Oral DRTF was administered for 4 weeks. The underlying mechanisms of the DRTF actions on disuse-induced osteoporosis are discussed. The results showed that DRTF treatment significantly increased the BMD and mechanical strength of tail-suspended rats. Enhanced bone turnover markers with HLU treatment were attenuated by DRTF administration. Deterioration of trabecular bone induced by HLU was prevented through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). The present study provides the first evidence that DRTF prevents bone loss induced by HLU treatment, indicating its potential application in the treatment of disuse-induced osteoporosis.Keywords:traditional chinese medicine;Drynariae Rhizoma;flavonoids;hindlimb unloading;osteoporosis
研究领域:
药理学
·
骨科
·
中医药
✓ 已验证
DOI
PubMed
高影响因子
Metabolites
·
2024
·Vol. 14
·期 8
·409
·
IF 3.4
Nana Chang,Xianping Yang,Xiaoqing Wang,Chao Chen,Chu Wang,Yang Xu,Hengyu Huang,Ye Wang
Drynaria roosii Nakaike, a fern widely distributed in China and some countries in Southeast Asia, is a commonly used herbal medicine in tonic diets and Chinese patented medicine. The metabolites of its dried rhizomes are easily affected by the epiphytic pattern, whether on rock tunnels (RTs) or tree trunks (TTs). The current research focused on rhizomes from these two patterns, RTs and TTs (further divided into subclasses TA, TB, TC, and TD, based on trunk differences) and conducted a widely targeted metabolomics analysis. A total of 1435 components were identified across 13 categories, with flavonoids, amino acids, and their derivative, lipids, identified as the main components. They accounted for 19.96%, 12.07%, and 12.14% of all metabolites, respectively. The top five flavonoids in TB were eriodicty-ol-7- O -(6″-acetyl)glucoside, quercetin-3- O -sophoroside (baimaside), dihydrochar-cone-4′- O -glucoside, morin, and hesperetin-7- O -glucoside, with relative contents 76.10, 24.20, 17.02, 15.84, and 14.64 times higher than in RTs. Principal component analysis revealed that samples with different epiphytic patterns clustered into five groups. The RT patterns revealed unique metabolites that were not detected in the other four epiphytic species (TA, TB, TC, and TD), including 16 authenticated metabolites: 1 alkaloid, 1 amino acid derivative, 7 flavonoids, 2 lignans, 1 lipid, 1 alcohol, 1 aldehyde, and 2 phenolic acids. These differences in epiphytic patterns considerably affected the accumulation of both primary and secondary metabolites. The comparison of diversity between RTs and TTs can guide the selection of a cultivation substance and the grading of collective rhizomes in the wild. This comprehensive analysis of D. roosii rhizome metabolites also offers fundamental insights for identifying active components and understanding the mechanisms underlying their potential pharmacological activities.
研究领域:
药理学
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植物学
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代谢组学
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中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Hui Jin,Ningning Jiang,Wenshu Xu,Zhongyuan Zhang,Yang Yang,Jingmin Zhang,Hui Xu
In this experimental study, we evaluated the protective effects and the safety of main flavanones derived from Rhizoma Drynariae (Gusuibu) in vitro and in vivo. The MTT assay showed that compared with vehicle treatment, treatment with such flavanones as neoeriocitrin, naringin, and naringenin significantly promoted the viability of osteocyte-like cells. Quantitative real-time PCR showed that neoeriocitrin and naringin significantly attenuated mRNA expressions of RANKL and SOST in osteocyte-like cells. In rats with retinoic acid-induced osteoporosis, total flavonoid of Rhizoma Drynariae (TFRD) , naringin, and naringenin significantly increased the number of trabeculae and improved trabecular bone structure compared with no treatment, without affecting liver and renal function. In addition, naringenin and naringin administration significantly increased bone mineral density of femur neck and femur shaft compared with the osteoporotic model rats. Western blot analysis showed that naringenin and naringin significantly attenuated protein expressions of bone resorption-related factors (TRAP, RANKL and RANK), and inhibited sclerostin expression compared with the osteoporotic model rats. On the other hand, naringin markedly increased protein expressions of ALP and PTH1R, and TFRD and naringenin also promoted PTH1R expression compared with the model rats. In conclusion, such flavanones as naringenin and naringin exhibited antiresorptive properties, and naringin particularly showed potential benefits for osteoporosis treatment.
研究领域:
药理学
·
骨科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yuxiao Zhao,Xiaofang Cai,Jian Sun,Wei Bi,Youcheng Yu
Ethnopharmacological relevance Rhizoma Drynariae , as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae . Aim of the study To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. Materials and methods The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo . The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Results Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-β signaling pathway to benefit bone regeneration. Conclusion The active components of TFRD modulate the TGF-β signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects.
研究领域:
药理学
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民族药理学
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骨生物学
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干细胞研究
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信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yujie Lu,Man Zhang,Jin Zhang,Min Jiang,Gang Bai
Ethnopharmacological relevance Psoralea corylifolia L. seeds ( P. corylifolia ), popularly known as Buguzhi in traditional Chinese medicine , are often used to treat osteoporosis in China. Psoralen (Pso) is the key anti-osteoporosis constituent in P. corylifolia , however, its targets and mechanism of action are still unclear. Aim of the study The purpose of this study was to explore the interaction between Pso and 17-β hydroxysteroid dehydrogenase type 2 (HSD17B2), an estrogen synthesis-related protein that inhibits the inactivation of estradiol (E2) to treat osteoporosis. Materials and methods Tissue distribution of Pso was analyzed by in-gel imaging after oral administration of an alkynyl-modified Pso probe (aPso) in mice. The target of Pso in the liver was identified and analyzed using chemical proteomics. Co-localization and cellular thermal shift assays (CETSA) were used to verify the key action targets. To detect the key pharmacophore of Pso, the interaction of Pso and its structural analogs with HSD17B2 was investigated by CETSA, HSD17B2 activity assay, and in-gel imaging determination. Target competitive test, virtual docking, mutated HSD17B2 activity, and CETSA assay were used to identify the binding site of Pso with HSD17B2. A mouse model of osteoporosis was established by ovariectomies, and the efficacy of Pso in vivo was confirmed by micro-CT, H&E staining, HSD17B2 activity, and bone-related biochemical assays. Results Pso regulated estrogen metabolism by targeting HSD17B2 in the liver, with the α, β-unsaturated ester in Pso being the key pharmacophore. Pso significantly suppressed HSD17B2 activity by irreversibly binding to Lys236 of HSD17B2 and preventing NAD + from entering the binding pocket. In vivo studies in ovariectomized mice revealed that Pso could inhibit HSD17B2 activity, prevent the inactivation of E2, increase levels of endogenous estrogen, improve bone metabolism-related indices, and play a role in anti-osteoporosis. Conclusions Pso covalently binds to Lys236 of HSD17B2 in hepatocytes to prevent the inactivation of E2, thereby aiding in the treatment of osteoporosis.
研究领域:
药理学
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民族药理学
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生物化学
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分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Ningning Jiang,Hui Jin,Kun Yang,Zhongyuan Zhang,Wenshu Xu,Xiaoxue Chen,Zhenhua Zhang,Hui Xu
The present study evaluated the in vitro effect of metformin (Met) and total flavonoids of Rhizoma Drynariae (TFRD) on osteoclasts, osteocytes, and osteoblasts at different stages. We also assessed the effect and mechanism of treatment with Met combined with TFRD on ovariectomy (OVX)-induced osteoporosis in rats. The results showed that Met combined with TFRD significantly promoted the migration of osteoprogenitor cells and stimulated the differentiation and maturation of osteoblast precursor cells. Furthermore, Met combined with TFRD treatment significantly inhibited the osteogenic inhibitor sclerostin (SOST)/dickkopf 1 (DKK1) protein expression and the osteoclast differentiation factor receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in osteocytes. In the in vivo study, Met combined with TFRD effectively reduced bone resorption markers levels, including type-I collagen carboxy-terminal peptide (CTX-1) and tartrate-resistant acid phosphatase (TRAP), and remarkably increased the bone formation marker propeptide of type I procollagen (PINP) level in the serum of rats with osteoporosis. Met combined with TFRD treatment improved bone mineral density (BMD), trabecular microstructure, and mechanical properties of osteoporotic rats. Mechanistically, Met combined with TFRD downregulated SOST and DKK1 levels, and upregulated Wnt10b, β-catenin, runt-related transcription factor 2 (Runx2) et al. Meanwhile, Met combined with TFRD treatment reduced the RANKL/OPG ratio, and reduced the receptor activator of nuclear factor-κB (RANK), nuclear factor of activated T cells c1 (NFATC1), and TRAP levels. In conclusion, Met combined with TFRD ameliorated bone mass in osteoporotic rats through regulating Wnt/β-catenin signaling pathway and OPG/RANKL/RANK axis.
研究领域:
药理学
·
骨科
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）