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Effects of Cistanches deserticola extract or estradiol valerate on urine and serum Ca and P of rats (n = 8); data were expressed as mean ± SD, * p < 0.05, ** p < 0.01, *** p < 0.001 versus ovariectomized model group; ## p < 0.01, ### p < 0.001 versus sham group.
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Given the limitations of existing therapeutic agents for treatment of postmenopausal osteoporosis, there still remains a need for more options with both efficacy and less adverse effects. Cistanche deserticola Y. C. Ma is known as a popular tonic herb traditionally used to treatment deficiency of kidney energy including muscle weakness in minority...
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... Chelates such as LHWCC showed a stronger influence on trabecular microstructure and calcium absorption than Ca 3 (PO 4 ) 2 and the co-administration of LHW and Ca 3 (PO 4 ) 2 . Bone microstructure, especially trabecular microstructure, plays an important role in monitoring calcium deposition in bone and characterizing bone growth and development levels [37,38]. Bone trabeculae have a certain shape and distance in the bone marrow cavity, cross-linking with each other to form a network structure, and are mainly responsible for maintaining bone strength, bearing loads, and hematopoietic functions [39]. ...
This study investigated the characteristics of Lactobacillus helveticus-derived whey-calcium chelate (LHWCC) and its effect on the calcium absorption and bone health of rats. Fourier-transform infrared spectroscopy showed that carboxyl oxygen atoms, amino nitrogen atoms, and phosphate ions were the major binding sites with calcium in LHWCC, which has a sustained release effect in simulated in vitro digestion. LHWCC had beneficial effects on serum biochemical parameters, bone biomechanics, and the morphological indexes of the bones of calcium-deficient rats when fed at a dose of 40 mg Ca/kg BW for 7 weeks. In contrast to the inorganic calcium supplement, LHWCC significantly upregulated the gene expression of transient receptor potential cation V5 (TRPV5), TRPV6, PepT1, calcium-binding protein-D9k (Calbindin-D9k), and a calcium pump (plasma membrane Ca-ATPase, PMCA1b), leading to promotion of the calcium absorption rate, whereas Ca3(PO4)2 only upregulated the TRPV6 channel in vivo. These findings illustrate the potential of LHWCC as an organic calcium supplement.
... Cistanche deserticola Y.C.Ma is a perennial parasitic herb, with approximately 22 kinds found globally. Experimental studies have shown that Cistanche deserticola Y.C.Ma has a protective effect on brain nerves, which can be beneficial in treating AD, PD, vascular dementia, and other diseases [141]. ...
Central nervous system (CNS) diseases seriously affect human life and health, currently, drugs used to treat CNS diseases mainly include receptor modulators and neurotransmitter inhibitors, which possess considerable side effects; accordingly, there is a need for efficacious drugs for clinical therapy. Traditional Chinese Medicines (TCMs) have a wide range of pharmacological effects on the CNS, especially as anti-CNS diseases. TCMs can enhance both non-specific and specific immune functions. Some TCMs can improve the adaptability of the body, enhance the body's resistance to various harmful stimuli, regulate pathological processes, and reverse the disordered function. TCMs and their active ingredients exhibit diverse pharmacological effects, including anti-neuritis, anti-oxidative stress regulation, and inhibition of cell apoptosis, with mechanisms possibly related to the regulation of the CNS function and restoring cell metabolism disorders. Based on literature from recent years, we summarize the neuroprotective effects of TCMs from the perspective of core pathological changes in the CNS and clinical applications. In addition, we integrated the progress of experimental research with regard to the pharmacological effects of TCMs on CNS. Current pharmacological investigations examining TCMs on CNS diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD), were reviewed to provide a reference and new concepts for further developing TCMs.
... Based on the theory of "kidney dominate bone", Cistanche Deserticola can be used as an alternative drug for the intervention of osteoporosis. 151 Cistanoside A (Cis A) is a phenylethanoid glycoside extracted from Cistanche Deserticola, which has the antioxidant effect of inhibiting ROS activity to inhibit apoptosis. 152 The expression of Wnt, β-catenin protein and autophagy were enhanced in OBs treated with Cis A. When Dickkopf-1 (DDK-1), an inhibitor of Wnt/β-catenin pathway, was used, it showed a significant decrease in LC3 fluorescence and a decrease in autophagosomes. ...
The maintenance of bone homeostasis is dynamically regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Abnormal differentiation of osteoclast and insufficient osteoblast production can cause bone diseases such as osteoporosis. As one of the highly conserved catabolic pathways in eukaryotic cells, autophagy plays an important role in maintaining cell homeostasis, stress injury repair, proliferation and differentiation. Numerous studies have found that autophagy activity is essential for the survival, differentiation and function of bone cells, and that regulation of autophagy can affect the metabolism of osteoblasts and osteoclasts, thus affecting bone homeostasis. Therefore, using autophagy as a theme, this review outlines the basic process of autophagy, the relationship between autophagy and osteoblasts and osteoclasts, and summarizes the latest research progress of common autophagic signaling pathways in osteoblasts and osteoclasts. The regulatory effects of protein molecules and natural compounds on the autophagy pathway of osteoblasts and osteoclasts discovered in current research are summarized and discussed. This will help to further clarify the mechanism of osteoporosis, understand the relationship between autophagy and osteoporosis, and propose new therapeutic strategies and new ideas for anti-osteoporosis.
... /": not have; "↑": up-regulation; "↓": down-regulation. the PI3K/Akt/mTOR, OPG/RANK/RANKL, Notch, and Hedgehog signaling pathways, are intricately associated with the onset and progression of osteoporosis(120)(121)(122)(123)(124)(125). However, studies regarding the impact of the lncRNA miRNA network loop on the regulation of these signaling pathways and its influence on the osteogenic differentiation of BMSCs remain unexplored in the existing literature. ...
Osteoporosis (OP) is characterized by a decrease in osteoblasts and an increase in adipocytes in the bone marrow compartment, alongside abnormal bone/fat differentiation, which ultimately results in imbalanced bone homeostasis. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts and adipocytes to maintain bone homeostasis. Several studies have shown that lncRNAs are competitive endogenous RNAs that form a lncRNA–miRNA network by targeting miRNA for the regulation of bone/fat differentiation in BMSCs; this mechanism is closely related to the corresponding treatment of OP and is important in the development of novel OP-targeted therapies. However, by reviewing the current literature, it became clear that there are limited summaries discussing the effects of the lncRNA–miRNA network on osteogenic/adipogenic differentiation in BMSCs. Therefore, this article provides a review of the current literature to explore the impact of the lncRNA–miRNA network on the osteogenic/adipogenic differentiation of BMSCs, with the aim of providing a new theoretical basis for the treatment of OP.
... The main pathogenesis is kidney deficiency, and clinical treatment is mainly to tonify the kidney and strengthen the bones, Chinese medicine has a definite curative effect in the treatment of PMOP . Research indicated that DC, as a Chinese medicine of tonifying kidney yang, could through different pathways such as the Wnt/β-catenin signaling pathway , bone metabolism , and RANKL/RANK/TRAF6 (Zhang et al. 2019) play a good therapeutic effect on PMOP. The pathogenesis of disease and the evaluation of drug efficacy lack systematic gene expression level analysis and evidence of interaction regulation. ...
Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis.
... Neuroprotection effect Echinacoside, acteoside Prohibiting the apoptosis of neurons [39][40][41] Bone metabolism regulation effect Echinacoside, acteoside, C. deserticola polysaccharides (CDP), cistanoside A Suppressing NF-κB and c-Fos pathways and downregulating NF-κB ligand receptor activator (RANKL) [42][43][44] Hepatoprotection activity Phenylethanoid glycosides (PhGs), CDP ...
As a famous tonic herb, Cistanches Herba is known for its broad medicinal functions, especially its hormone balancing, anti-aging, anti-dementia, anti-tumor, anti-oxidative, neuroprotective, and hepatoprotective effects. This study aims to provide a comprehensive bibliometric analysis of studies on Cistanche and to identify research hotspots and frontier topics on the genus. Based on the metrological analysis software CiteSpace, 443 Cistanche related papers were quantitatively reviewed. The results indicate that 330 institutions from 46 countries have publications in this field. China was the leading country in terms of research importance and number of publication (335 articles). In the past decades, studies on Cistanche have mainly focused on its rich active substances and pharmacological effects. Although the research trend shows that Cistanche has grown from an endangered species to an important industrial plant, its breeding and cultivation continue to be important areas for research. In the future, the application of Cistanche species as functional foods may be a new research trend. In addition, active collaborations among researchers, institutions, and countries are expected.
... Tumor necrosis factor receptor-associated factor 6 (TRAF6), a ubiquitin ligase in the RING family, is a key bridging molecule of the NF-κB pathway and plays an important role in the regulation of osteoclast formation. Previous studies have shown that TRAF6-deficient mice have bone abnormalities and osteosclerosis [44]. TRAF6 is essential for RANKL signaling and osteoclast differentiation. ...
The ubiquitination-proteasome system (UPS) is crucial in regulating a variety of cellular processes including proliferation, differentiation, and survival. Ubiquitin protein ligase E3 is the most critical molecule in the UPS system. Dysregulation of the UPS system is associated with many conditions. Over the past few decades, there have been an increasing number of studies focusing on the UPS system and how it affects bone metabolism. Multiple E3 ubiquitin ligases have been found to mediate osteogenesis or osteolysis through a variety of pathways. In this review, we describe the mechanisms of UPS, especially E3 ubiquitin ligases on bone metabolism. To date, many E3 ubiquitin ligases have been found to regulate osteogenesis or osteoclast differentiation. We review the classification of these E3 enzymes and the mechanisms that influence upstream and downstream molecules and transduction pathways. Finally, this paper reviews the discovery of the relevant UPS inhibitors, drug molecules, and noncoding RNAs so far and prospects the future research and treatment.
... Traditional Chinese medicine (TCM) has achieved unique and impressive advantages in treating PMO in China [13][14][15][16]. TCM believes that the pathogenesis of PMO is associated with the deficiency in kidney function, accompanied by spleen and stomach weakness, insufficient blood supply to liver, and blood stasis. ...
Background:
Postmenopausal osteoporosis (PMO) is the most prevalent metabolic bone disease in women. Yishen Zhuanggu (YSZG) decoction and Caltrate D600 reportedly affects bone formation. This study aimed to investigate the efficacy and mechanism of YSZG decoction combined with Caltrate D600 in PMO treatment.
Methods:
Ovariectomy-induced PMO rat model was treated with YSZG or/and Caltrate D600 for 12 weeks. Femur bone mineral density (BMD), osteoporosis-related protein expression, and serum parameters were measured. Pathological features of femur bone tissues were observed using hematoxylin and eosin staining. Serum levels of oxidative stress parameters were measured using corresponding commercial kits. The mRNA and protein expression of FoxO3a, Wnt, and β-catenin was detected using qRT-PCR and western blotting.
Results:
The BMD and ultimate load of PMO rats were increased after treatment with YSZG. YSZG treatment promoted the bone trabeculae formation of PMO rats. YSZG treatment also induced bone differentiation and suppress oxidative stress in PMO rats, evidenced by the increased BALP, Runx2, OPG, SOD, and CAT levels, as well as the decreased TRACP 5b, RANKL, ROS, and MDA levels. Additionally, YSZG treatment downregulated the FoxO3a expression and upregulated the levels of Wnt and β-catenin in PMO rats. Caltrate D600 addition showed an auxiliary effect for YSZG.
Conclusion:
YSZG decoction exerts the antiosteoporotic effect on PMO by restraining the FoxO3a expression and activating the Wnt/β-catenin pathway, which has an impressive synergistic effect with Caltrate D600.
... The serum RANK concentrations in Sham, OVX, OVX+ICA and OVX+E2 followed a similar trend to BGP, being up to 1339 pg/mL in OVX group and 935-1117 pg/mL in other treatments ( Figure 3B). However, both ovariectomy and ICA or E2 administration did not significant change the concentration of serum RANKL ( Figure 3C), a biomarker that can be bound to RANK to enhance osteoclastogenesis (34). Unlike RANKL, OPG, as another ligand of RANK, in the serum of OVX rats was significantly down-regulated to 1572 pg/mL by 31% lower than Sham group (p < 0.05) ( Figure 3D). ...
Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced bone loss, which has been shown an association with an altered gut microbiota (GM). Gut microbiota-bone axis has been recognized as a crucial mediator for bone homeostasis. Icariin (ICA) is an effective agent to delay bone loss by regulating the bone homeostasis. Thus, we hypothesize that ICA can prevent bone loss by modulating GM and regulating metabolite alterations. The effects of ICA on bone metabolism improvement in ovariectomized (OVX) rats and their relationships with the GM and fecal metabolites were investigated. Micro-computed tomography (micro-CT) and hematoxylin-eosin (HE) staining showed a typical bone boss in OVX group, while ICA or estradiol (E2) administration exhibited positive effects on bone micro-architecture improvement. The GM such as Actinobacteria, Gammaproteobacteria, Erysipelotrichi, Erysipelotrichales, Enterobacteriales, Actinomycetales, Ruminococcus and Oscillospira significantly correlated to serum bone Gla-protein (BGP), receptor activator of nuclear factor-κB (RANK), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG) and tartrate resistant acid phosphatase (TRACP). Further t-test revealed a substantial variation of the GM and fecal metabolites in different treatments. Among them, Lachnoclostridium, Butyricimonas, Rikenella, Paraprevolla, Adlercreutzia, Enterorhabdus, Anaerovorax, Allobaculum, Elusimicrobium, Lactococcus, Globicatella and Lactobacillus were probably the key microbial communities driving the change of bile acid, amino acid and fatty acid, thereby leading to an improvement of PMOP. The significant up-regulation of L-Saccharopine, 1-Aminocyclohexadieneacid and linoleic acid after ICA administration suggested important contributions of amino acid and fatty acid metabolisms in the prevention and treatment of PMOP. Taken together, our study has provided new perspectives to better understand the effects of ICA on PMOP improvement by regulating GM and the associated fecal metabolites. Our findings contribute to develop ICA as a potential therapy for PMOP.
... The extracts of these Chinese herbal medicines (Jing extracts) have been characterized by chemical constituent analysis with LC/MS and NMR (Cai et al., 2020;Hu et al., 2021) as well as highperformance liquid chromatogram-gas chromatography fingerprint analysis (Liu et al., 2008) (Table 2; Supplementary Figure S7). Astragalus with supplemental calcium significantly improved bone mineral density and bone metabolism in ovariectomized rats Kang et al. (2013) The extracts from Myristica fragrans, Astragalus, and Poria cocos ameliorated alcohol-induced acute liver toxicity Yimam et al. (2016) Cistanche deserticola Y. C. Ma (Cistanche deserticola) Chinese: Rou Cong Rong Cistanche deserticola has antiosteoporotic activity in type I osteoporotic rats Zhang et al. (2021) and type II osteoporotic mice Wang et al. (2021) Cistanche deserticola possessed hepatoprotective activity against chronic hepatic injury induced by alcohol Guo et al. (2016) Dioscorea polystachya Turcz. (Dioscorea polystachya, Chinese yam) Chinese: Shan Yao Dioscorea spongiosa prevents glucocorticoid-induced osteoporosis in rats Han et al. (2016) and aging-induced osteoporosis Tikhonova et al. (2015) Dioscorea polystachya extracts have protective effects against alcohol-induced gastric ulcers in mice Byeon et al. (2018) Lycium barbarum L. (Lycium barbarum, Chinese wolfberry or Goji berry) Chinese: Gou Qi ...
Traditional Chinese medicine (TCM) has been practiced in the treatment of bone diseases and alcoholism. Chronic excessive alcohol use results in alcohol-induced bone diseases, including osteopenia and osteoporosis, which increases fracture risk, deficient bone repair, and osteonecrosis. This preclinical study investigated the therapeutic effects of TCM herbal extracts in animal models of chronic excessive alcohol consumption-induced osteopenia. TCM herbal extracts (Jing extracts) were prepared from nine Chinese herbal medicines, a combinative herbal formula for antifatigue and immune regulation, including Astragalus, Cistanche deserticola, Dioscorea polystachya, Lycium barbarum, Epimedium, Cinnamomum cassia, Syzygium aromaticum, Angelica sinensis, and Curculigo orchioides. In this study, Balb/c male mice were orally administrated alcohol (3.2 g/kg/day) with/without TCM herbal extracts (0.125 g/kg, 0.25 g/kg, or 0.5 g/kg) by gavage. Our results showed that after 50 days of oral administration, TCM herbal extracts prevented alcohol-induced osteopenia demonstrated by μ-CT bone morphological analysis in young adults and middle-aged/old Balb/c male mice. Biochemical analysis demonstrated that chronic alcohol consumption inhibits bone formation and has a neutral impact on bone resorption, suggesting that TCM herbal extracts (Jing extracts) mitigate the alcohol-induced abnormal bone metabolism in middle-aged/old male mice. Protocatechuic acid, a natural phenolic acid in Jing extracts, mitigates in vivo alcohol-induced decline of alkaline phosphatase (ALP) gene expression in the bone marrow of Balb/c male mice and in vitro ALP activity in pre-osteoblast MC3T3-E1 cells. Our study suggests that TCM herbal extracts prevent chronic excessive alcohol consumption-induced osteopenia in male mice, implying that traditional medicinal plants have the therapeutic potential of preventing alcohol-induced bone diseases.
