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.

Characterization of three novel stem rot pathogens and their antagonistic endophytic bacteria associated with Cistanche deserticola.

Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.

The protective effect and mechanism of glycosides of cistanche deserticola on rats in middle cerebral artery occlusion (MCAO) model.

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.

The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

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.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral vaccine adjuvant delivery enhancing both the mucosal and systemic immunity.

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.

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.

The gut-liver axis perspective: Exploring the protective potential of polysaccharides from Cistanche deserticola against alcoholic liver disease.

The primary objective of this study is to investigate the potential mechanism behind the protective effect of Cistanche deserticola polysaccharides (CP) against alcoholic liver disease (ALD). Multiple chromography techniques were employed to characterize CP from polysaccharide, the molecular weight distribution of polysaccharides, monosaccharide composition, isomeric hydrogen and isomeric carbon, in order to clarify the material basis of CP. To create the ALD mouse model, we utilized the well-established Lieber-DeCarli alcoholic liquid feed method. Findings from the study revealed that CP administration resulted in significant improvements in intestinal permeability, upregulation of barrier proteins expression, and reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mouse liver and serum. Additionally, CP treatment reduced the presence of inflammatory cytokines both in serum and liver while enhancing the activity of antioxidant enzymes in the liver. Furthermore, CP effectively reduced alcohol-induced oxidative damage by downregulating Keap1 protein levels in the liver, leading to increased expression of Nrf2 protein. The 16S rDNA sequencing results revealed that CP significantly restored the intestinal microbiota composition in ALD mice. These findings establish a strong association between gut microbiota and liver injury indicators, highlighting the potential of CP in preventing and treating ALD by modulating the gut-liver axis.

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.

Cistanche deserticola Polysaccharide Reduces Inflammation and Aging Phenotypes in the Dermal Fibroblasts through the Activation of the NRF2/HO-1 Pathway.

Dermal fibroblasts maintain the skin homeostasis by interacting with the epidermis and extracellular matrix. Their senescence contributes to functional defects in the skin related to aging. Therefore, there is an urgent need for novel therapeutic agents that could inhibit fibroblast senescence. In this study, we investigated the effects of Cistanche deserticola polysaccharide (CDP), a natural anti-inflammatory component, on the progression of senescence in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were cultured in passages, and highly senescent cells were selected as senescent cells. CDP treatment increased the cell proliferation in senescent NHDFs and decreased the proportion of senescence-associated-ß-galactosidase-positive cells. The treatment suppressed the senescence-related secretory phenotype, and reactive oxygen species (ROS) production was reduced, alleviating H2O2-induced oxidative stress. CDP mitigated ROS formation via the nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway in senescent cells and was involved in the suppression of upstream p-extracellular signal-regulated kinase. These results indicate that CDP is an antioxidant that can alleviate age-related inflammation and may be a useful compound for skin anti-aging.

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.

Diversity and potential plant growth promoting capacity of seed endophytic bacteria of the holoparasite Cistanche phelypaea (Orobanchaceae).

Salt marshes are highly dynamic, biologically diverse ecosystems with a broad range of ecological functions. We investigated the endophytic bacterial community of surface sterilized seeds of the holoparasitic Cistanche phelypaea growing in coastal salt marshes of the Iberian Peninsula in Portugal. C. phelypaea is the only representative of the genus Cistanche that was reported in such habitat. Using high-throughput sequencing methods, 23 bacterial phyla and 263 different OTUs on genus level were found. Bacterial strains belonging to phyla Proteobacteria and Actinobacteriota were dominating. Also some newly classified or undiscovered bacterial phyla, unclassified and unexplored taxonomic groups, symbiotic Archaea groups inhabited the C. phelypaea seeds. γ-Proteobacteria was the most diverse phylogenetic group. Sixty-three bacterial strains belonging to Bacilli, Actinomycetes, α-, γ- and ß-Proteobacteria and unclassified bacteria were isolated. We also investigated the in vitro PGP traits and salt tolerance of the isolates. Among the Actinobacteria, Micromonospora spp. showed the most promising endophytes in the seeds. Taken together, the results indicated that the seeds were inhabited by halotolerant bacterial strains that may play a role in mitigating the adverse effects of salt stress on the host plant. In future research, these bacteria should be assessed as potential sources of novel and unique bioactive compounds or as novel bacterial species.

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.

Combined Metabolome and Transcriptome Analysis Highlights the Host's Influence on Cistanche deserticola Metabolite Accumulation.

The medicinal plant Cistanche deserticola Ma (Orobanchaceae) is a holoparasitic angiosperm that takes life-essential materials from Haloxylon ammodendron (C. A. Mey.) Bunge (Amaranthaceae) roots. Although many experiments have been conducted to improve the quality of C. deserticola, little attention has been paid to the host's influence on metabolite accumulation. In this study, transcriptomic and metabolomic analyses were performed to unveil the host's role in C. deserticola's metabolite accumulation, especially of phenylethanoid glycosides (PhGs). The results indicate that parasitism by C. deserticola causes significant changes in H. ammodendron roots in relation to metabolites and genes linked to phenylalanine metabolism, tryptophan metabolism and phenylpropanoid biosynthesis pathways, which provide precursors for PhGs. Correlation analysis of genes and metabolites further confirms that C. deserticola's parasitism affects PhG biosynthesis in H. ammodendron roots. Then we found specific upregulation of glycosyltransferases in haustoria which connect the parasites and hosts. It was shown that C. deserticola absorbs PhG precursors from the host and that glycosylation takes place in the haustorium. We mainly discuss how the host resists C. deserticola parasitism and how this medicinal parasite exploits its unfavorable position and takes advantage of host-derived metabolites. Our study highlights that the status of the host plant affects not only the production but also the quality of Cistanches Herba, which provides a practical direction for medicinal plant cultivation.

[Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification].

This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 µg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.

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.