Ferroptosis pathways: Unveiling the neuroprotective power of cistache deserticola phenylethanoid glycosides.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease. AIM OF THE STUDY: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS. MATERIALS AND METHODS: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia. RESULTS: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe2+ efflux and regulating mitochondrial Fe2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer). CONCLUSIONS: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.

The role of Cistanches Herba and its ingredients in improving reproductive outcomes: A comprehensive review.

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.

Network pharmacological study and in vitro studies validation-Molecular dynamics simulation of Cistanche deserticola in promoting periodontitis and bone remodeling.

OBJECTIVE: Periodontitis is a chronic infectious disease, characterized by loss of alveolar bone and supporting tissues. Cistanche deserticola(Cd), a local medicinal herb in Xinjiang, possesses favorable biological characteristics and potential applications. Our aim is to investigate the remodeling properties of Cd extract and elucidate the specific mechanisms underlying its therapeutic effects on periodontitis, by employing a combination of basic experimental and network pharmacology approaches. METHODS: Firstly, UHPLC-QTOF-MS analysis was conducted on Cd extract to identify its main components, with several compounds were identified by standard. Subsequently, in vitro studies were performed using the Cd extract on MC3T3-E1 cells. Cell proliferation viability was assessed using CCK-8 and apoptosis assays, while ALP and ARS staining and quantitative experiments, qRT-PCR, and Western blot assays were employed to evaluate the osteogenic differentiation capability. Network pharmacology analysis was then carried out using the identified compounds to establish a database of Cd components and targets, along with a database of periodontitis. The intersection of these databases revealed the network relationship between Cd components-mapped genes-signaling pathways. KEGG/GO pathway analysis of the targets was performed to filter potential enriched pathways. PPI/CytoHubba protein interaction network analysis was utilized to identify hub genes. Molecular docking and molecular dynamics simulations were employed to analyze the docking and interaction between core gene and Cd components. RESULTS: We detected 38 major components in the Cd extract, with Echinacoside, Acteoside, Tubuloside A, and Cistanoside A undergoing standard substance verification. In vitro studies indicated that the Cd, at concentrations below 100 µg/ mL, did not affect cell proliferation and inhibited apoptosis. Osteogenesis assays demonstrated that Cd at concentrations of 1 µg/ mL, 10 µg/ mL, and 100 µg/ mL significantly promoted the osteogenic differentiation ability of MC3T3-E1 cells. It also notably upregulated the mRNA and protein levels of Alp, Bmp2, Runx2, and Opn, and the optimal concentration was 10 µg/mL. Network pharmacology results revealed the network relationship between Cd's components, crossed targets and signaling pathways. Combined with KEGG/GO pathway analysis and PPI/CytoHubba protein interaction network analysis. The key pathway and hub genes of Cd regulating periodontitis are both related to hypoxia pathway and HIF-1α. Molecular docking results showed a strong binding affinity between Cd compounds and hub genes, and molecular dynamics simulation results indicated the stability of the complexes formed between HIF-1α and several Cd compounds. CONCLUSION: Cistanche deserticola exhibits a notable capacity to promote bone regeneration, and its mechanism of action in regulating periodontitis is associated with the hypoxia signaling pathway. HIF-1α may serve as a potential core gene. Future research will focus on exploring the mechanism of Cd in intervene periodontitis and promoting bone remodeling in hypoxic environment.

Tubuloside B, a major constituent of Cistanche deserticola, inhibits migration of hepatocellular carcinoma by inhibiting Hippo-YAP pathway.

BACKGROUND: Studies have shown that phenylethanoid glycosides (PhGs) have multiple pharmacological effects such as anti-inflammatory, hepatoprotective or neuroprotective functions, whereas their anti-tumor effects are rarely studied. Tubuloside B (Tub B) is a PhG isolated from Cistanche deserticola, a traditional Chinese medicine. To date, there is a lack of comprehensive research regarding the biological activity of Tub B. PURPOSE: The subject of the current study was to investigate the anti-hepatocellular carcinoma (HCC) cell activity and the underlying mechanism of Tub B. METHODS: We evaluated the in vitro anti-migratory effect of Tub B by scratch and transwell assays. RNA-seq was employed to identify the differential genes by Tub B. Besides, the functional mechanism of Tub B was investigated by distinct molecular biology techniques including immunofluorescent staining, quantitative PCR, as well as western blot analysis. Subsequently, we utilized Hep3B cells for in vivo metastasis assays through spleen injection and evaluated the anti-migratory effect of Tub B in hepatocellular carcinoma (HCC). RESULTS: Tub B exhibited in vitro and in vivo inhibition of HCC cell migration. Tub B decreased the expression of transcriptional target genes downstream of the Hippo pathway, including CTGF, CYR61, and N-cadherin as determined by RNA-seq. Furthermore, mechanistic studies confirmed that Tub B increased phosphorylation of YAP at S127, which contributes to YAP cytoplasmic localization. Additionally, overexpression of YAP abrogated Tub B-induced inhibition of HCC migration and the mRNA levels of CTGF, CYR61, and N-cadherin. CONCLUSIONS: Taken together, these results illustrated that Tub B demonstrated great potential in inhibiting migration of HCC, and a portion of its impact can be attributed to the modulation of the Hippo-YAP pathway.

Structure characterization of polysaccharides from Cistanche deserticola and their neuroprotective effects against oxidative stress in slow transit constipation mice.

Oxidative stress-induced enteric neuropathy is an important factor in slow transit constipation (STC). Cistanche deserticola crude polysaccharides (CDCP) are natural antioxidants with various biological activities. We prepared CDCP through water-extract and alcohol-precipitation methods. The structural characteristics of CDCP were analyzed by infrared spectroscopy and methylation analysis. The results showed that CDCP was primarily composed of (1 â†’ 4)-linked glucans with minor amounts of pectic polysaccharides. Different doses of CDCP (100, 200, and 400 mg/kg) were administered to loperamide-induced STC mice to explore the therapeutic effects of CDCP. Compared with the untreated group, CDCP treatment significantly improved constipation symptoms, relevant gut-regulating peptides levels, colonic pathological damage, and colonic myenteric nerons injury. CDCP enhanced the antioxidant capacity by decreasing Malondialdehyde (MDA) content, increasing Superoxide Dismutase (SOD) activity and Reduced Glutathione (GSH) content. CDCP significantly reduced oxidative stress-induced injury by preserving mitochondrial function in the colonic myenteric plexus. Furthermore, the neuroprotective effects of CDCP might be associated with the Nrf2/Keap1 pathway. Thus, our findings first revealed the potential of CDCP to protect the colonic myenteric plexus against oxidative stress-induced damage in STC, establishing CDCP as promising candidates for natural medicine in the clinical management of STC.

Cistanche deserticola improves ovariectomized-induced osteoporosis mainly by regulating lipid metabolism: Insights from serum metabolomics using UPLC/Q-TOF-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola (C. deserticola) is an edible and traditional medicine widely used in China, which has been confirmed to be effective in the treatment of postmenopausal osteoporosis (PMOP). Despite its proven efficacy, the exact role of C. deserticola in bone metabolism and its underlying mechanism has remained unclear. AIM OF THE STUDY: In this research, we employed an in vivo model utilizing ovariectomized (OVX) rats to characterize the anti-osteoporotic activity and metabolic mechanism of the ethanol extract of C. deserticola (CHE). MATERIALS AND METHODS: Fifty female Sprague-Dawley (SD) rats were randomly divided into five groups including sham operation group, model group, 0.1 g/kg estradiol valerate (EV) group as the positive control, low (0.6 g/kg) and high (1.2 g/kg) dosage CHE groups. Biochemical parameter analyses and histopathological experiments were conducted to assess the pharmacodynamic effects. Metabolomic analysis was conducted on serum samples to examine the metabolic profiles, identify potential biomarkers, and elucidate the metabolic pathways associated with CHE in OVX rats. RESULTS: CHE treatment demonstrated significant anti-osteoporosis activity by regulating serum biochemical markers of bone turnover, improving cancellous bone structure, and reversing the decrease in bone mineral density. Furthermore, the clinical equivalent dose group (CHL) achieved superior overall outcomes. The main interventions of CHE on OVX rats involved the modulation of several key pathways, including steroid hormone biosynthesis, arachidonic acid metabolism, tyrosine and tryptophan metabolism, biotin metabolism, regulation of TRP channels by inflammatory mediators, primary bile acid biosynthesis, regulation of lipolysis in adipocytes, and bile secretion. 23 potential efficacy-related biomarkers within the metabolic network were identified. Among them, long-chain unsaturated fatty acids (eg. DHA and docosapentaenoic acid), steroid hormones, amino acids and carbohydrates were strongly correlated with bone resorption and formation markers. Additionally, it was observed four pathways (nucleotide, carbon, amino acid, and lipid metabolism) were implicated in the effects of CHE. CONCLUSION: This study demonstrates that CHE improves bone loss in PMOP mainly through regulating lipid metabolism pathways, which provides an evidence base for CHE treatment of PMOP.

Cistadesertosides B-E, Four New Diastereomeric Lignan Glycosides from the Stems of Cultural Cistanche deserticola in Tarim Desert.

Four previously undescribed diastereomeric lignan glycosides, namely cistadesertosides B-E (1-4) were isolated from the stems of cultural Cistanche deserticola in Tarim desert. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses, including IR, HR-ESI-MS, 1D and 2D NMR, circular dichroism (CD) data and chemical degradation. The in vitro anti-inflammatory activity of the isolates was also investigated. It showed that compounds 3 and 4 exhibited potential effects with IC50 values of 21.17 µM and 26.97 µM, respectively (positive control quercetin, IC50 , 10.01 µM).

Optimization of Chemical Extraction Conditions of Dietary Fiber from Cistanche deserticola Residues and Its Structural Characteristics and Physicochemical and Functional Properties.

Cistanche deserticola residues are by-products of the industrial production of Cistanche deserticola, which are currently often discarded, resulting in the waste of resources. In order to achieve the efficient utilization of Cistanche deserticola, dietary fiber from Cistanche deserticola residues was extracted chemically and the optimization of the extraction conditions was performed, using the response surface methodology to study the effects of the NaOH concentration, extraction temperature, extraction time, and solid-liquid ratio on the yield of water-soluble dietary fiber (SDF). The structural, physicochemical, and functional properties of the dietary fiber were also investigated. The results showed that the optimal conditions were as follows: NaOH concentration of 3.7%, extraction temperature of 71.7 °C, extraction time of 89.5 min, and solid-liquid ratio of 1:34. The average yield of SDF was 19.56%, which was close to the predicted value of 19.66%. The two dietary fiber types had typical polysaccharide absorption peaks and typical type I cellulose crystal structures, and the surface microstructures of the two dietary fiber types were different, with the surface of SDF being looser and more porous. Both dietary fiber types had good functional properties, with SDF having the strongest water-holding capacity and the strongest adsorption capacity for nitrite, cholesterol, sodium cholate, and glucose, while IDF had a better oil-holding capacity. These results suggest that Cistanche deserticola residues are a good source of dietary fiber and have promising applications in the functional food processing industry.

Transcriptomic analysis the mechanisms of anti-osteoporosis of desert-living Cistanche herb in ovariectomized rats of postmenopausal osteoporosis.

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.

Microbiome and metabolome integrally reveal the anti-depression effects of Cistanche deserticola polysaccharides from the perspective of gut homeostasis.

Polysaccharides are one of the active components of Cistanche deserticola (CD). Cistanche deserticola polysaccharides (CDPs) significantly regulate gut microbiota, immune activity, and neuroprotective functions. However, it merely scratches the surface that the anti-depression effects of CDPs. We aimed to demonstrate the anti-depression effects of CDPs and the underlying mechanisms from the perspectives of gut homeostasis by behavioral evaluations and applying integrally microbiome, metabolome, and molecular biology. CDPs showed significant effects on improving abnormal behaviors of depressed rats. Additionally, CDPs maintained Th17/Treg balance and modulated gut immunity of depressed rats. Comprehensive microbiome and metabolome analysis showed that CDPs significantly ameliorated abundances of beneficial bacteria, and increased the contents of SCFAs, consequently maintaining gut homeostasis. Besides, the anti-depression effects of CDPs involved in amino acid metabolism including BCAAs, glutamine, etc., maintaining metabolic balance. The current findings provide not only deep understanding of depression focusing on gut, but also evidence about the anti-depression effects of CDPs, broadening clinic applications of CDPs. Of note, the present study is of significance in a long run, in terms of providing novel strategies and protocols for revealing mechanisms of anti-depression drugs, and for the discovery of new antidepressants and functional foods from natural products.

Effects of different processing (Paozhi) on structural characterization and antioxidant activities of polysaccharides from Cistanche deserticola.

In this study, five polysaccharides were extracted from processed Cistanche deserticola. The processing included crude product, enzymatic hydrolysis, hot air drying, stir-baking with wine and high-pressure steaming, and these polysaccharides were named as CP-CDPs, EH-CDPs, HAD-CDPs, SBW-CDPs and HPS-CDPs, respectively. The structural characteristics and biological activities were explored. The results showed that processing changed properties of C. deserticola polysaccharides. CP-CDPs had the highest brightness value L*(93.84) and carbohydrate content (61.27 %). EH-CDPs had minimum Mw (1531.50 kDa), while SBW-CDPs had maximum Mw (2526.0 kDa). Glucose was major predominant monosaccharide in CP-CDPs (89.82 %), HAD-CDPs (79.3 %), SBW-CDPs (59.41 %) and HPS-CDPs (63.86 %), while galactose was major monosaccharide in EH-CDPs (29.44 %). According to SEM, SBW-CDPs showed compact structures, while HPS-CDPs and HAD-CDPs had similar looser structure than SBW-CDPs; meanwhile, CP-CDPs showed irregular agglomeration shape and EH-CDPs was dense blocky shape. The AFM showed SBW-CDPs had the largest molecular chain than other polysaccharides. When scavenging activity reaching 50 %, the concentrations of CP-CDPs, EH-CDPs, HAD-CDPs, SBW-CDPs, HPS-CDPs are 2.25, 0.25, 0.75, 1.8 and 1.5 mg/mL, respectively. This study sheds light on the effects of traditional Chinese medicine processing on characteristics, bioactivities of C. deserticola polysaccharides, and provides the basis for applications in food and pharmaceutical industries.

Quantitative analysis and hepatoprotective mechanism of Cistanche deserticola Y. C. Ma against alcohol-induced liver injury in mice.

Cistanche deserticola Y. C. Ma (CD), known as "desert ginseng", has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.

Phenylethanoid glycosides extract from Cistanche deserticola ameliorates atherosclerosis in apolipoprotein E-deficient mice and regulates intestinal PPARγ-LXRα-ABCA1 pathway.

OBJECTIVES: This study was aimed to evaluate the protective effects of phenylethanoid glycosides extract from Cistanche deserticola against atherosclerosis and its molecular mechanism. METHODS: Total phenylethanoid glycosides were extracted and purified from C. deserticola, and the C. deserticola extract (CDE) was used to treat a mice model of atherosclerosis. KEY FINDINGS: CDE containing 81.00% total phenylethanoid glycosides, with the contents of echinacoside and acteoside being 31.36% and 7.23%, respectively. A 13-week of CDE supplementation (1000 mg/kg body weight/day) significantly reduced atherosclerotic lesions in the aortic sinus and entire aorta in ApoE-/- mice fed with a high-fat diet. In addition, varying doses of CDE (250, 500 and 1000 mg/kg body weight/day) lowered plasma total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels. Transcriptomic analysis of the small intestine revealed the changes enriched in cholesterol metabolic pathway and the activation of Abca1 gene. Further validation using real-time quantitative PCR and western blot confirmed that CDE significantly increased the mRNA levels and protein expressions of ABCA1, LXRα and PPARγ. CONCLUSIONS: Our results demonstrate the beneficial effects of C. deserticola on atherosclerotic plaques and lipid homeostasis, and it is, at least partially, by activating PPARγ-LXRα-ABCA1 pathway in small intestine.

Rapid Determination of Polysaccharides in Cistanche Tubulosa Using Near-Infrared Spectroscopy Combined with Machine Learning.

BACKGROUND: Cistanche tubulosa, as a homology of medicine and food, not only has a unique medicinal value but also is widely used in healthcare products. Polysaccharide is one of its important quality indicators. OBJECTIVE: In this study, an analytical model based on near-infrared (NIR) spectroscopy combined with machine learning was established to predict the polysaccharide content of C. tubulosa. METHODS: The polysaccharide content in the samples determined by the phenol-sulfuric acid method was used as a reference value, and machine learning was applied to relate the spectral information to the reference value. Dividing the samples into a calibration set and a prediction set using the Kennard-Stone algorithm. The model was optimized by various preprocessing methods, including Savitzky-Golay (SG), standard normal variate (SNV), multiple scattering correction (MSC), first-order derivative (FD), second-order derivative (SD), and combinations of them. Variable selection was performed through the successive projections algorithm (SPA) and stability competitive adaptive reweighted sampling (sCARS). Four machine learning models were used to build quantitative models, including the random forest (RF), partial least-squares (PLS), principal component regression (PCR), and support vector machine (SVM). The evaluation indexes of the model were the coefficient of determination (R2), root-mean-square error (RMSE), and residual prediction deviation (RPD). RESULTS: RF performs best among the four machine learning models. R2c （calibration set coefficient of determination） and RMSEC （root mean square error of the calibration set）, %, were 0.9763. and 0.3527 for calibration, respectively. R2p （prediction set coefficient of determination）, RMSEP （root mean square error of the prediction set）, %, and RPD were 0.9230, 0.5130, and 3.33 for prediction, respectively. CONCLUSION: The results indicate that NIR combined with the RF is an effective method applied to the quality evaluation of the polysaccharides of C. tubulosa. HIGHLIGHTS: Four quantitative models were developed to predict the polysaccharide content in C. tubulosa, and good results were obtained. The characteristic variables were basically determined by the sCARS algorithm, and the corresponding characteristic groups were analyzed.

Research progress on polysaccharide components of Cistanche deserticola as potential pharmaceutical agents.

Cistanche deserticola is a traditional and precious Chinese herbal medicine, known as "desert ginseng", with anti-inflammatory, anti-oxidant, improving immunity, nourishing the kidneys and other pharmacological effects. Its chemical components mainly include phenylethanol glycosides, iridoids, polysaccharides and volatile components, among which polysaccharides have received extensive attention due to their biological activities such as regulating immune activity, anti-aging, anti-spleen deficiency and antitumor. In recent years, a large number of research have been carried out on the extraction and isolation, chemical structure analysis and biological activity of Cistanche deserticola polysaccharides. The methods of polysaccharide extraction mainly include traditional extraction method, ultrasonic assisted method, microwave assisted method and enzyme assisted method, etc. The extracted polysaccharides were analyzed by chemical methods including methylation, acid hydrolysis and Smith degradation and spectroscopy methods such as NMR and IR. A variety of polysaccharides with new structures were obtained, and some polysaccharides with known structures were also investigated for their biological activities and their structure-activity relationships. However, the relationship between polysaccharides structure and their biological activities is still unclear due to the large number of polysaccharide components, their complex structures and the lack of systematic research and analysis on them. It is expected that the subsequent study of polysaccharide structure and active conformational relationship will be highly valuable for the application of Cistanche deserticola in pharmaceutical sciences and health food.

Cistanche Deserticola for Regulation of Bone Metabolism: Therapeutic Potential and Molecular Mechanisms on Postmenopausal Osteoporosis.

Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass, destruction of bone microstructure, increased brittleness and therefore fracture. At present, the main treatment of Western medicine is drug therapy such as bisphosphonates, calcitriol, vitamin D, etc. However, long-term use of these drugs may bring some adverse reactions. Chinese herbal medicine Cistanche deserticola could regulate bone metabolism by promoting osteoblast activity and inhibiting osteoclast activity with low toxicity and adverse reactions. Therefore, Cistanche deserticola has attracted increasing attention for its efficacy in the prevention and treatment of osteoporosis in recent years. Here we present a literature review of the molecular pathways involved in osteoporosis and the effects of Cistanche deserticola on bone metabolism. Our objective is to clarify the mechanism of Cistanche deserticola in the treatment of osteoporosis.

Chemical composition and adjuvant properties of the macromolecules from cultivated Cistanche deserticola Y. C. Ma as an immunopotentiator.

The study aims to investigate the constituents, adjuvant effects, and underlying mechanisms of purified polysaccharides from cultivated Cistanche deserticola (C. deserticola). Two macromolecules designated as CCDP-1 (26.5 kDa) and CCDP-2 (32.3 kDa) from C. deserticola were respectively identified as carbohydrate-lignin complexes with 44.1 % and 43.8 % lignin. CCDP-1 and CCDP-2 were composed of glucose, rhamnose, galactose, arabinose, and mannose respectively in the molar ratios of 7.22: 5.98:2.51:1.81:1.00 and 6.57:8.48:4.20:2.72:1.00. An in vitro experiment revealed that endotoxin-free CCDP-1 and CCDP-2 promoted splenocyte proliferation without cytotoxicity, but CCDP-2 induced dendritic cell (DC) maturation more efficiently than CCDP-1. An in vivo experiment suggested that CCDP-2 enhanced OVA-specific antibody production, antigen-specific T-cell activation, IFN-γ production, IL-4 production, and DC activation. Notably, CCDP-2 elicited a Th1-biased response. Mechanically, CCDP-2 upregulated CD40, CD80, CD86, and MHC II, facilitated allogeneic T-cell proliferation and Th1/Th2 cytokines, improved IFN-γ, IL-12, IL-6, and TNF-α production, and decreased endocytosis from DCs in vitro. Blocking assays indicated that TLR2 and TLR4 were the membrane receptor candidates of DCs. Western blot implied that CCDP-2 with the immune-enhancing activities were involved in the activation of MAPKs and NF-κB pathways in a dose-/time-related manner and could be employed as a more balanced Th1/Th2 adjuvant for vaccine exploitation.

Integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology to probe distinctions between the stems of Cistanche deserticola and C. tubulosa based on antidepressant activity.

Cistanches Herba (CH), as a nutritional and functional supplement used in food and health care products for centuries, consists of the stems of Cistanche deserticola and C. tubulosa. Our previous studies confirmed that the stems of C. tubulosa exerted advantageous antidepressant effect. However, whether the difference in the phytochemical compositions between the stems of C. deserticola and C. tubulosa would lead to diverse bioavailability and accompanying antidepressant effects remain unclear, as well as their specific bioactive compounds and underlying mechanism. In this study, a series of comparative studies showed that the antidepressant activity of C. tubulosa extract (CTE) was stronger than that of the C. deserticola extract (CDE), which was accompanied with the discovery of 10 differential markers from 52 identified compounds between CTE and CDE, and different pharmacokinetic behaviors of 9 prototype and 4 metabolites belonging to the glycosides between the CTE-treated and CDE-treated group in normal and depressive rats were simultaneously found by a validated UPLC-QTRAP-MS/MS method. Subsequently, network pharmacology prediction, in vitro and in vivo experiment verification from these differential markers further revealed that 7 compounds were confirmed to contribute to the antidepressant action of CH by inhibiting neuronal apoptosis mediated by mitochondrial function and activation of the AKT/GSK3ß signaling pathway, synchronously indicating most of those, with higher bioavailability in vivo after CTE administration, that were responsible for the stronger antidepressant effect of CTE over CDE. Hence, the integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology provide new insights into the applications of CH from different botanical origins against depression.

Glycosylation of Aromatic Glycosides by a Promiscuous Glycosyltransferase UGT71BD1 from Cistanche tubulosa.

Multiple-glycosylated glycosides are a major source of bioactive leads. However, most of the currently reported glycosyltransferases (GTases) mainly catalyze glycosylation of aglycones without sugar group substitution. GTases accepting diverse glycosides as substrates are rarely reported. In this article, a new GTase UGT71BD1 was identified from Cistanche tubulosa, a desert herb plant abundant with various phenylethanoid glycosides (PhGs). Interestingly, UGT71BD1 showed no activity toward the aglycone of PhGs. Instead, it could catalyze the further glycosylation of PhG compounds to produce new phenylethanoid multiglycosylated glycosides, including the natural rarely separated tetraglycoside PhGs. Extensive assays found the unprecedented substrate promiscuity of UGT71BD1 toward diverse glycosides including flavonoid glycosides, stilbene glycosides, and coumarin glycosides, performing further mono- or diglycosylation with efficient conversion rates. Using UGT71BD1, six multiglycosylated glycosides were prepared and structurally identified by NMR spectroscopy. These products showed enhanced pharmacological activities compared with the substrates. Docking, dynamic simulation, and mutagenesis studies identified key residues for UGT71BD1's activity and revealed that the sugar modules in glycosides play crucial roles in substrate recognition, thus partly illuminating the unusual substrate preference of UGT71BD1 toward diverse glycosides. UGT71BD1 could be a potential enzyme tool for glycosylation of diverse glycosides.

Microbiome-metabolomics deciphers the effects of Cistanche deserticola polysaccharides on aged constipated rats.

Chronic constipation is an extremely common gastrointestinal disorder that severely affects the life quality of the elderly. As an edible food and therapeutic medicine, Cistanche deserticola (CD) has been widely used not only as food in daily life, but also as a medicine to treat constipation. As the main component in CD, polysaccharide shows great potentials in improving constipation in the elderly. In this study, 16S rRNA analysis and fecal metabolomics were applied to investigate the impacts of constipation in an aged rat model, as well as the regulatory effects and the underlying mechanisms of CD polysaccharide (CDPS). Firstly, a classic constipation model of aged rats was constructed. The behavioral indicators of the rats were analyzed, providing behavioral correlations at the macro level. Meanwhile, the levels of SOD, GSH-Px, MDA, and CAT in serum samples of the rats were assessed. Additionally, the changes of gut microbiota, fecal metabolites and corresponding metabolic pathways in the aged constipated rats were demonstrated. On top of this, inter-and inner-layer networks of "behavioral indicators - intestinal bacteria - metabolites" were constructed to visually demonstrate the relationships among differential indicators. We found that CDPS significantly regulated the abnormalities of the behavioral indexes, the microbial richness and diversity, and the metabolite profiles that were induced by constipation in the aged rats. From the intestinal microbiological point of view, CDPS significantly increased the prevalence of beneficial bacteria while reducing the potentially pathogenic bacterial population. In terms of metabolomics, a total of 16 metabolites were finally identified as potential biomarkers of constipation in the aged rats. The mechanisms of CDPS were mainly involved in metabolic energy and the synthesis of amino acids. The current findings not only deepen our understanding about constipation in the elderly from the perspectives of microbiome and metabolomics, but also lay a solid foundation for the applications of polysaccharides in constipation in the elderly, the discovery of new medicines for constipation, and improving the life quality of the elderly.