Effects of Cistanches Herba polysaccharides on rats with constipation-predominant irritable bowel syndrome / 中国药房

OBJECTIVE To investigate the effects of Cistanches Herba polysaccharides （abbreviated as CDPS） on rats with constipation-predominant irritable bowel syndrome （IBS-C）. METHODS SD rats were divided into control group （20 rats） and modeling group. The modeling group was given 2 mL of normal saline at 0-4 ℃ intragastrically （once a day， for 14 consecutive days） to induce IBS-C model. After modeling， model rats were grouped into model group， positive control group （mosapride citrate， 1.35 mg/kg）， CDPS low-dose group （50 mg/kg） and CDPS high-dose group （100 mg/kg）， with 20 rats in each group. Administration groups were given corresponding drug solution intragastrically， and control group and model group were given a constant volume of water intragastrically， once a day， for 28 consecutive days. The fecal water content， serum content of 5-hydroxytryptamine （5-HT）， and charcoal powder propulsion rate of rats were determined in each group；the pathological morphology of colon tissue was observed， and mRNA and protein expressions of nerve growth factor （NGF） and tropomyosin receptor kinase A （TrkA） in colon tissue were detected. RESULTS Compared with control group， the fecal water content and carbon powder propulsion rate in the model group were decreased significantly （P＜0.05）； the rupture of mucosal muscle layer in colon tissue， significant infiltration of inflammatory cells and cellular edema were observed； the content of 5-HT in serum， and relative mRNA and protein expressions of NGF and TrkA were increased significantly （P＜0.05）. Compared with model group， the fecal water content and carbon powder propulsion rate of rats were increased significantly in administration groups （P＜0.05）， and pathological changes of colon tissue were relieved significantly， while the content of 5-HT in serum， the mRNA and protein expressions of NGF and TrkA in colon tissue were decreased significantly （P＜0.05）； among them， the above indicators inthe positive control group and CDPS high-dose group were generally close to those in the control group （P＞0.05）. CONCLUSIONS CDPS can alleviate the symptoms of IBS-C rats， which may be related to the inhibition of NGF/TrkA signaling pathway.

Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification / 中国中药杂志

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.

High-quality Formation of Cistanches Herba： A Review / 中国实验方剂学杂志

With the continuous development of traditional Chinese medicine （TCM）， the requirement for the quality of Chinese medicines has become increasingly higher since they have been widely used in clinical practice. Chinese medicinal materials are the material basis for the inheritance and development of TCM， and their quality directly affects the clinical efficacy. Studying the quality of Chinese medicinal materials is the key to ensure the quality and realize the large-scale application. As one of rare Chinese medicinal materials， Cistanches Herba has the functions of tonifying kidney yang， invigorating blood and essence， moistening intestines to relieve constipation. High-quality Cistanches Herba is characterized by glossy appearance， high density， fleshy and soft texture， and sweet taste. With the reduction of wild resources， the products from cultivated Cistanche deserticola or C. tubulosa become dominant on the market of Cistanches Herba. The cultivation areas are widely distributed， mainly concentrated in Gansu， Inner Mongolia， and Xinjiang. However， the cultivated products have varied quality due to the differences in germplasm， producing region， cultivation method， harvesting， and processing. According to the theories of quality evaluation based on morphological characteristics and excellent appearance indicating high quality， this paper reviewed the literature on the quality evaluation， growth， development， and processing of Cistanches Herba in the last decade to explore the main factors （genetic characteristics， environmental conditions， and harvesting and processing factors） affecting the quality of Cistanches Herba. The review aims to explore the factors for the high quality and provide a reference for the producing region screening， directional cultivation， and production of Cistanches Herba.

Determination of monosaccharide composition of polysaccharide and free monosaccharides in Cistanches Herba by ion chromatography-integral pulsed amperometry / 药学学报

Polysaccharides and free monosaccharides are important active components in Cistanches Herba, which have functions of anti-aging and immunological activity regulation. The study of monosaccharide composition in polysaccharide and free monosaccharide can lay a foundation for the study of primary structure, spatial structure of Cistanche polysaccharide and biological activity of Cistanches Herba. In this study, a method of water extraction and alcohol precipitation was used to extract Cistanche polysaccharide. Trifluoroacetic acid was selected as the hydrolytic acid for polysaccharide hydrolysis. An orthogonal experimental method is established. Three levels of acid concentration, hydrolysis temperature and hydrolysis time were selected to investigate the optimal hydrolysis condition. The optimal hydrolysis condition was 0.08 mol·L-1 trifluoroacetic acid hydrolysis at 100 ℃ for 3 h. The free monosaccharides of Cistanches Herba were extracted by water extraction. The established ion chromatogram integrated pulsed amperometry method can efficiently separate 11 monosaccharides in a short time. The method has good repeatability and high sensitivity, methodological experiment results meet the requirements of quantitative determination. It can accurately determine the monosaccharide composition of Cistanche polysaccharide and free monosaccharide content. Ion chromatography does not require derivatization operation and the pre-treatment steps are simple. This method can measure fructose, but PMP derivation-HPLC method can't. The monosaccharide composition of Cistanche polysaccharide include fucose, arabinose, rhamnose-galactose, glucose, xylose, mannose, fructose, ribose and glucuronic acid, among which the contents of glucose and fructose are relatively high. The free monosaccharides in the water extract of Cistanches Herba include glucose, fructose and mannose.

Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacology / 中国中药杂志

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.

Safety and Toxicological Assessment of Allantoin Extract from Cistanches Herba / 中国实验方剂学杂志

Objective: To evaluate the safety of allantoin extract from Cistanches Herba,so as to provide scientific support for subsequent utilization and development of allantoin extract from Cistanches Herba.Method: According to the national standard procedures and methods in food safety and toxicological evaluation,a series of toxicological studies on allantoin extract from Cistanches Herba were conducted,including genetic toxicity and subacute toxicity tests.Result: In the Ames test,with or without mammalina liver microsomal enzymes (S9),allantoin extract from Cistanches Herba in 40,200,1 000,5 000 μg·dish-1 dose range for four bacteria showed no dose-dependent increase.In the micronucleus test,there was no statistically significant difference among each dose group and the negative control group.In the test of mouse sperm aberration,there was no significant difference in the sperm aberration rate among the allantoin extract group and the negative control group.The results of three genotoxicity tests were all negative,indicating no genotoxicity in allantoin extract.The results of 30 days test showed no death and abnormal clinical sign in rats of control group and each dose group (1.100,0.550,0.275 g·kg-1).The body weight,food intake,weekly and total food utilization,weight increment,organ/body ratios,blood biochemical indexes and blood routine indexes had no significant difference among the control group and dose groups.There was no abnormal pathological change in heart,liver,spleen,lung,kidney and testicle of rats in treatment group.Conclusion: Allantoin extract from Cistanches Herba is a non-toxic substance without any genetic toxicity but with a high edible safety.This study provides scientific experimental basis for its safety.

Transformation pathways in methanol of echinacoside, a principal effective ingredient of Cistanches Herba / 中国中药杂志

Echinacoside (ECH) is one of the active ingredients in Cistanche Herba and the principal effective component of Memoregain© as well. Moreover, a new agent namely Naoqing Zhiming tablet, derived from ECH has been licensed for clinical trials. However, the knowledge regarding the stability of is limited, till now, initiating a significant barrier for its further development along with the clinical trials. Herein, we aim to in depth characterize the transformation pattern of ECH in methanol. When ECH was stored in methanol, two primary products (P1 and P2) could be observed in HPLC chromatogram. A home-made automated fraction collector was configured via employing two 2-phase/6-port electronic valves to prepare P1 and P2. Following ¹H-NMR and LC-MS/MS assays, P1 and P2 were unambiguously identified as acteoside and cistanoside A, respectively. Moreover, the existences of cis-ECH, cis-acteoside, and cis-cistanoside A were claimed after careful analysis of the ¹H-NMR spectra of ECH, P1 and P2. Above all, the primary transformation pathways of ECH in methanol included methylation as well as hydrolysis, and mild transformation could also be initiated by cis/trans- configuration transferring for the caffeoyl group. The findings obtained in current study are envisioned to provide useful insight for the further development of ECH and the impurity detection of Naoqing Zhiming tablet. Moreover, the automated fraction collector configured in current study is able to serve as a versatile tool for the collection of signals-of-interest within phytochemical evaluations and impurity isolation.

Pharmacological targets identification and efficacy analysis of phenylethanoid glycosides from Cistanches Herba based on “target fishing” strategy / 中草药

Objective Cistanches Herba is a kind of tonic traditional Chinese medicine with several therapy effects including tonifying kidney-yin, anti-dementia, anti-aging and relaxing bowel. Phenylethanoid glycosides (PhGs) are the major effective components in C. tubulosa. However, there were no further studies on molecular pharmacologic mechanisms due to its complex components and mechanism diversity of action in PhGs till to now. The aim of this study was to investigate the target protein groups and related mechanisms associated with PhGs in anticerebral ischemia-reperfusion injury. Methods The middle cerebral artery occlusion (MCAO) model was established in rats, and the protective effects of PhGs on cerebral ischemia-induced injuries were determined. A kind of solid bead whose surface was cross-linked with PhGs was prepared to capture the target proteins from brain tissue lysates. The target proteins were further identified with LC-MS/MS. Results PhGs significantly inhibited cerebral ischemia-induced injuries by reducing ischemia size and rat behavioral scores and elevated the SOD levels in rat brain tissues. Eighteen target proteins were identified based on “target fishing” strategy and divided into 9 kinds according to their biological functions, including anti-oxidation, ion channel, immunoregulation, cell survival and cytoskeleton, etc. Conclusion These findings reveal the potential pharmacological mechanisms of PhGs in anti-dementia, fatigability alleviating, anti-tumor, immunoloregulation, etc, and also present a promising technology for investigating the complicated pharmacological mechanisms of traditional Chinese medicine.

Ancient Literature Textual Research on Medicinal and Edible History of Cistanches Herba / 中国药学杂志

Cistanches Herba, which mainly grows in the arid or semiarid areas in northwest China, is one of the precious tonic Chinese material medica. It has been traditionally used as a nutritious food in China for thousands of years. Ancient literature with regard to the variety origin, producing areas, property and flavor, traditional effect and toxicity, usage and dosage, and edibility of Cistanches Herba are summarized in this review. The origin plants are Cistanche deserticola Y.C. Ma and Cistanche salsa (C.A. Mey.) G. Beck. The producing areas and present effect of Cistanches Herbaare the same as those in the ancient literature. It is often made into oral pills for various adult consumptive diseases. It is contraindicated in cases of essence deficiency with yang going upward adversely and diarrhea. The dietotherapy history of Cistanches Herba in China can be traced back to the Northern and Southern Dynasties (420-589). Cistanches Herba braised with mutton or sheep kidneys is a time-honored dish in China to alleviate fatigue. This work is committed to providing literature evidence for further research on the raw materials of Cistanches Herba as health foods.

Fingerprint comparative analysis of Cistanche deserticola Y.C. Ma and Cistanche tubulosa (Schrenk) Wight / 中国药学杂志

OBJECTIVE: To establish the UPLC fingerprint of Cistanche deserticola Y.C. Ma and Cistanche tubulosa (Schrenk) Wight. METHODS: The UPLC fingerprints of 10 batches of C. deserticola and C. tubulosa were determined on an ACQUITY UPLC® BEH C18 column (2.1 mm×50 mm, 1.7 μm) eluted with the mobile phase consisting of 0.2% formic acid solution and acetonitrile in gradient mode at a flow rate of 0.4 mL·min-1, the column temperature was 40℃, and the detection wavelength was set at 240 nm. The chemical attribution of the fingerprint was determined by reference substance comparison method. RESULTS: The common mode of the UPLC fingerprint of C. deserticola and C. tubulosa was set up under the established conditiom. There were 15 common peaks in the fingerprints of 10 samples, five of which were identified. The similarities varied from 0.667 to 0.905 and from 0.249 to 0.991 for Cistanche deserticola Y.C. Ma and Cistanche tubulosa (Schrenk) Wight, respectively. There was significant difference in the fingerprints between C. deserticola and C. tubulosa. CONCLUSION: The method is simple and reliable, which can be readily utilized for distinguishing C. deserticola from C. tubulosa and their quality control.

Cistanches Herba: Chemical Constituents and Pharmacological Effects / 中草药·英文版

Cistanches Herba, known as "Ginseng of the desert", is authenticated from the dried succulent stems of Cistanche deserticola and Cistanche tubulosa. As a famous remedy in China for tonic the kidney, it is used to treat "kidney-deficiency syndrome"-induced diseases such as infertility, forgetfulness, hearing lost, chronic constipation, etc.. As various biological activities, including anti-aging, antioxidant, estrogenic, anti-osteoporotic, and anti-inflammation effects, have been discovered, here we reviewed Cistanches Herba in biological characteristics, chemical constituents, and pharmacological activities.

Study on material basis of increasing efficacy of wine-fried Cistanches Herba by UPLC-Q-TOF/MS / 中草药

Objective: Cistanche Herba was studied to explain the differences of the material basis before and after wine-fried processing, and to approach the scientific connotation for wine-fried Cistanches Herba with the functions of warming and tonifying kidney-Yang and avoiding side effects of slippery bowel diarrhea. Methods: The chemical analysis of crude and processed Cistanche Herba was performed by ultra-performance liquid chromatography method (UPLC) coupled with quadrupole time of flight mass spectrometry (Q-TOF/MS). The principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) were used to distinguish the content variation between crude and processed Cistanche Herba. Results: The material basis for increased efficacy of wine-fried Cistanche Herba was studied for the first time. The contents of echinacoside, acteoside, β-sitosterol, daucosterol, sucrose, and inosine increased. Especially, the contents of echinacoside and acteoside increased significantly. The contents of 8-epiloganic acid, succinic acid, and geniposide decreased in the wine-fried Cistanche Herba. The most obvious chemical markers, such as echinacoside, acteoside, cistanoside A, and geniposide, could be used as index components to distinguish the crude and processed Cistanche Herba. Conclusion: The study is important for the processing principle of the processed Cistanche Herba and provides an important scientific basis for clarifying the effective material basis and avoiding the side effects of the wine-fried Cistanche Herba.