穿山龙苗医

To prevent confusing Dioscorea nipponica (DN), an Oriental medicine, with Dioscorea quinquelobata (DQ) and Dioscorea septemloba (DS), a simple and accurate quantitative analysis method using HPLC combined with ultraviolet (UV) detection was developed and verified with UPLC-QTOF/MS through identification of five saponin glycosides: protodioscin (1), protogracillin (2), pseudoprotodioscin (3), dioscin (4), and gracillin (5). The newly developed analysis method showed sufficient reproducibility (<1.91%) and accuracy (92.1%–102.6%) and was able to identify DN based on the presence of compound 3 (13.821 ± 0.037 mg/mL) and the absence of 5. Compound 1, which is present in DN at a relatively high level (159.983 ± 0.064 mg/mL), was also an important marker for identification. Among the three species, DN showed the strongest activation of apoptotic signaling in osteosarcoma cells, while the four compounds detected in DN showed IC50 values of 6.43 (1), 10.61 (2), 10.48 (3), and 6.90 (4). In conclusion, the strong inhibitory effect of DN against osteosarcoma was confirmed to be associated with 1 and 4, which is also related to the quantitative results. Therefore, the results of this study might provide important information for quality control related to Oriental medicine.

Introduction Dormant cancer cells, capable of reactivating from the G0 phase, drive tumor recurrence and therapy resistance. Current clinical strategies targeting dormancy remain limited. This study evaluates Punica granatum peel (PGP) and Dioscorea Nipponica (DN) for their ability to sustain dormancy in lung cancer cells and inhibit reactivation. Methods Dormancy was induced in A549 and H460 lung cancer cells via contact inhibition or serum deprivation. Subcutaneous and orthotopic xenograft mouse models were employed. Cells and mice were treated with PGP, DN, or their combination. SYBR Green assays, flow cytometry, and immunoblotting assessed DNA synthesis, cell cycle phases, and protein expression (p27, SKP2, cMYC, AURORA A, SUPT16H, SSRP1). Results Both PGP and DN significantly inhibited DNA synthesis and cell cycle re-entry (G0-to-G1 transition) in vitro. In vivo, tumor volume and weight decreased by 26–50% (p < 0.05) in treated mice. Treatments upregulated p27 while downregulating SKP2, cMYC, AURORA A, SUPT16H, and SSRP1. No synergistic effect was observed, but additive efficacy (Combination Index ≈1) was noted at a 10:1 PGP:DN ratio. Discussion PGP and DN sustain dormancy by modulating key cell cycle regulators, highlighting their potential to reduce recurrence and combat drug resistance. These findings underscore the therapeutic promise of traditional Chinese medicines in managing dormant cancer cells. Future studies should identify active compounds and validate mechanisms in advanced models.

This study reported the isolation and identification of bioactive compounds from Dioscorea nipponica Makino, a plant used in traditional medicine for various ailments. Nine compounds were isolated, including a new compound named as diosniposide E, which was elucidated by analyzing its ^1H-NMR, ^13C-NMR, DEPT, COSY, HMBC and MS data and comparing them with data available in literature. The other eight compounds were identified as known compounds. Theoretical calculations of energy and the generation of a molecular electrostatic potential surface map were employed to assess the antioxidant capacity of nine compounds, the calculation results exhibited that compounds 5 and 6 had strong antioxidant capacities. To further evaluate the antioxidant activities of the investigated compounds, the DPPH and ABTS assays were conducted. The results from the DPPH scavenging activity test revealed that compounds 4 – 6 exhibited enhanced scavenging activities compared to L-ascorbic acid, while displaying similar efficacy to trolox. Moreover, the ABTS scavenging activities of compounds 4 – 6 were found to surpass those of L-ascorbic acid and trolox. In terms of α-glucosidase inhibition, compounds 3 and 4 displayed remarkable inhibitory activities that surpassed the effects of acarbose. Additionally, compound 2 exhibited potent anticholinesterase activities, outperforming donepezil. This research provides insights into the potential bioactive compounds present in Dioscorea nipponica Makino and may contribute to its use in traditional medicine.

Dioscorea nipponica Makino, a perennial twining herb with medicinal importance, has a disjunctive distribution in the Sino-Japanese Floristic Region. It has a long history in traditional Chinese medicine, with demonstrated efficacy against various health conditions. However, the limited genomic data and knowledge of genetic variation have hindered its comprehensive exploration, utilization and conservation. In this study, we undertook low-coverage whole genome sequencing of diverse D. nipponica accessions to develop both plastome (including whole plastome sequences, plastome-derived SSRs and plastome-divergent hotspots) and nuclear genomic resources (including polymorphic nuclear SSRs and single-copy nuclear genes), as well as elucidate the intraspecific phylogeny of this species. Our research revealed 639 plastome-derived SSRs and highlighted six key mutational hotspots (namely CDS ycf1, IGS trnL-rpl32, IGS trnE-trnT, IGS rps16-trnQ, Intron 1 of clpP, and Intron trnG) within these accessions. Besides, three IGS regions (i.e., ndhD-cssA, trnL-rpl32, trnD-trnY), and the intron rps16 were identified as potential markers for distinguishing D. nipponica from its closely related species. In parallel, we successfully developed 988 high-quality candidate polymorphic nuclear SSRs and identified 17 single-copy nuclear genes for D. nipponica, all of which empower us to conduct in-depth investigations into phylogenetics and population genetics of this species. Although our phylogenetic analyses, based on plastome sequences and single-copy nuclear genes revealed cytonuclear discordance within D. nipponica, both findings challenged the current subspecies classification. In summary, this study developed a wealth of genomic resources for D. nipponica and enhanced our understanding of the intraspecific phylogeny of this species, offering valuable insights that can be instrumental in the conservation and strategic utilization of this economically significant plant.

The rhizome of Dioscorea nipponica Makino (RDN) is a widely used herbal medicine, which has significant anti-inflammatory activities on various inflammatory diseases. However, the bioactive compositions responsible for the anti-inflammatory activity of RDN are still unknown. This study aimed to identify the anti-inflammatory bioactive compounds in RDN using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS), quantitative analysis of multiple components by single marker (QAMS) and chemometric methods. Firstly, an HPLC-Q/TOF-MS method was employed for identification of bioactive steroidal saponins in RND, and a total of twelve steroid saponins were identified. Then, QAMS method was employed to determine the contents of seven bioactive steroidal saponins, including protodioscin, protogracillin, methyl protodioscin, pseudoprotodioscin, pseudoprogracillin, dioscin and gracillin in RND samples using dioscin as the reference analyte. The anti-inflammatory effects of RDN samples were then evaluated by inhibition of NO production in LPS-induced RAW264.7 cells. Furthermore, chemometric methods, including Pearson correlation analysis and partial least squares regression (PLSR) were employed to investigate the correlations between chemical components and anti-inflammatory activities, and explore the potential anti-inflammatory bioactive compounds of RDN. The results indicated that protodioscin, dioscin and gracillin were selected as the major anti-inflammatory compounds in RND. The further verification experiments showed that protodioscin, dioscin and gracillin exhibited great inhibition on NO production with IC50 values (the half maximal inhibitory concentration) of 0.712 μM, 0.469 μM and 0.815 μM, respectively. They also significantly reduced the levels of TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. The present study provided evidences for the anti-inflammatory activity of RND and identification of the anti-inflammatory components in RDN.

Dioscorea nipponica Makino is an optimal candidate to develop the diosgenin industry in North China. Due to its increasing demand in the medicine industry, it is urgent to apply new biotechnological tools to foster breeds with desirable traits and enhanced secondary metabolite production. The production of useful metabolites by the in vitro cultured rhizomes can be explored successfully for utilization by various food and drug industries. In this study, we reported callus formation and plantlet regeneration of the medicinal plant D. nipponica. Explants of leaves, stem segments and rhizomes of aseptic seedlings were cultured on Murashige and Skoog (MS) medium containing various combinations of auxin and cytokinin to find the optimal PGRs of each type of explant for callus induction and shoot regeneration of D. nipponica. The paraffin section technique was also used to observe of the morphogenesis of callus and adventitious bud. Explants of seeds and rhizomes formed calli at high frequency in all lines we examined. However, the explant of leaves rarely formed callus. Three kinds of callus were detected during the induction phase. Here, we describe three types of callus (Callus I–III) with different structure characteristics. Greenish in color and a nodule-like protrusion surface (Callus type III) were arranged more closely of cells with less interstitial substance, cell differentiation ability stronger than other callus types. The optimum combination was the maximum shoot differentiation frequency of 90% in callus derived from seeds cultured on MS medium with 2.0 mg L−16-BA + 0.2 mg L−1NAA. The shoot differentiation frequency (88.57%) of rhizome-induced callus was obtained by the combination of MS medium supplemented with 3.0 mg L−16-BA + 2.0 mg L−1NAA. 1/2 MS medium plus 0.5 mg L−1NAA resulted in a higher root regeneration frequency of 86.70%. In vitro propagated plantlets with healthy roots were domesticated and transplanted into small plastic pots containing sterile soil rite under greenhouse conditions with 80% survivability. Bud differentiation is mostly of exogenous origin, mostly occurring on the near callus surface. Therefore, it may be surmised that in vitro morphogenesis of D. nipponica is mainly caused by indirect organogenesis (adventitious bud).

Dioscorea nipponica Makino is widely used in traditional Chinese medicine to treat gouty arthritis. Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). HE staining was used to detect the histopathologic changes of the synovial tissue of joint. Immunohistochemical method was used to detect the protein expressions of P-38, p-P38, JNK, p-JNK, ERK1/2, p-ERK1/2, MEK1/2, p-MEK1/2, MKK4, p-MKK4, ICAM1, VCAM1, and PPARγ in the synovial tissue of joint. Realtime PCR and WB methods were used to detect the mRNA and protein expressions of PPARγ and AdipoR2 in the synovial tissue of joint. The contents of CXCL1 and ADP in the blood serum were measured by Elisa method. Our study showed that RDN could improve the situation of the synovial tissue, reduce the protein expressions of MKK4, p-MEK1/2, p-JNK, p-ERK1/2, ICAM1. They could also decrease the content of CXCL1 and increase the content of ADP in the blood serum. RDN has good effect of anti-inflammation. This is in part realized by influencing MAPK signalling pathway. It provides a new visual angle to reveal the mechanism of RDN to treat GA.

Studying the biotransformation of natural products by intestinal microflora is an important approach to understanding how and why some medicines—particularly natural medicines—work. In many cases, the active components are generated by metabolic activation. This is critical for drug research and development. As a means to explore the therapeutic mechanism of Dioscorea nipponica (DN), a medicinal plant used to treat myocardial ischemia (MI), metabolites generated by intestinal microflora from DN were identified, and the cardioprotective efficacy of these metabolites was evaluated. Our results demonstrate that diosgenin is the main metabolite produced by rat intestinal microflora from DN. Further, our results show that diosgenin protects the myocardium against ischemic insult through increasing enzymatic and nonenzymatic antioxidant levels in vivo and by decreasing oxidative stress damage. These mechanisms explain the clinical efficacy of DN as an anti-MI drug.

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Introduction. The original article presents the results of an experimental study conducted using the method of high-performance thin-layer chromatography (HPTLC) on plant samples – rhizomes with roots of Dioscorea caucasica Lipsky and Dioscorea nipponika Makino. These species of Dioscorea are used in various fields of medicine as fungicides, antimicrobials, and anti-sclerotic agents. The HPTLC method is used at the screening stage of plant samples for preliminary identification and densitometric quantitative determination of diosgenin in plant extracts. Aim. Development of a HPTLC methodology for quantitative assessment of diosgenin content after acid hydrolysis of extracts in air-dried raw materials – rhizomes with roots of Dioscorea caucasica Lipsky and Dioscorea nipponika Makino. Materials and methods. The extracts were obtained by preliminary degreasing and depigmentation of air-dried rhizomes with roots of the studied Dioscorea species using high-purity dichloromethane, followed by double extraction. The first extraction was carried out in a 50 % aqueous solution of isopropanol with ultrasonication, followed by acid hydrolysis of O-glycosidic bonds and evaporation. The second extraction was carried out by redissolving the dry residue in methanol; it was purified from suspended particles by filtration through syringe filters with a perforation diameter of 20 μm. HPTLC was performed on a «CAMAG» (Switzerland) apparatus using HPTLC Aluminum sheets Silica gel 60 F254 20 × 20 cm, which were cut to a size of 20 × 10 cm. Results and discussion. After performing scanning densitometry at 366 and 542 nm, it was established that the chromatography of methanol extracts in a toluene-chloroform-acetone solvent system (2 : 8 : 2 v/v) allows for satisfactory separation and subsequent densitometric quantitative determination of diosgenin. The tracks of plant extracts from the rhizomes and roots of Dioscorea caucasica Lipsky and Dioscorea nipponika Makino were compared with a standard sample of diosgenin. Conclusion. The study found that the content of the steroid sapogenin diosgenin in air-dried Dioscorea nipponica Makino raw material (286,4–296,3 μg/g) slightly exceeds its content in Dioscorea caucasica Lipsky raw material (257–277,1 μg/g). The quantitative values obtained, calculated separately for peak height and area, show good convergence, confirming the correctness of the method. The developed method of high-performance thin-layer chromatography with densitometric detection of diosgenin can be recommended for routine quantitative analysis of this compound in plant raw materials.

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INTRODUCTION Dioscorea species, which contain abundant steroidal saponins, have been used as folk medicines or raw materials to synthesise steroid drugs. OBJECTIVE To establish a rapid chemotaxonomic method that will comprehensively resolve confusions about genetic relationships of genus Dioscorea. METHODS A comprehensive strategy using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) was firstly proposed to evaluate the chemotaxonomy of 12 species (27 taxa) from China by hierarchical cluster analysis (HCA) based on the variations of the identified metabolites. RESULTS Twenty-eight secondary metabolites (mainly steroidal saponins) were identified. The MSn fragmentation patterns of DA (a new acetylated steroidal saponin at C-7 position) were firstly reported. Moreover, eight major steroidal saponins were further quantified simultaneously by UPLC-QTOF-MS method. According to HCA results, D. bulbifera L. was distinguished with species of sect. Stenophora Uline for pennogenin-type steroidal saponins. Dioscorea zingiberensis exhibited far distance from other members of sect. Stenophora Uline for two unique saponins. Dioscorea banzhuana may be reclassified into sect. Stenophora. Dioscorea nipponica subsp. rosthornii and D. collettii var. hypoglauca might be separated from their original subspecies/varieties as new species, respectively. CONCLUSION The chemotaxonomic method was successfully applied in the study of genetic relationships of Dioscorea species. This study not only enhanced the understanding of chemical constituents, but also laid basic theoretical foundations for the rational utilisation and chemotaxonomy of genus Dioscorea.

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It has been reported that colitis is one of risk factors in colorectal cancer (CRC). Intervention of intestinal inflammation and in the early stage of tumorigenesis is of great significance to control the incidence and mortality of CRC. In recent years, natural active products of traditional Chinese medicine have been confirmed that they had made great progress in disease prevention. Here, we showed that Dioscin, a natural active product of Dioscorea nipponica Makino, inhibited initiation and tumorigenesis of AOM/DSS-induced colitis-associated colon cancer (CAC), including alleviating colonic inflammation, improving intestinal barrier function and decreasing tumor burden. In addition, we also explored the immunoregulatory effect of Dioscin on mice. The results showed that Dioscin modulated M1/M2 macrophages phenotype in spleen and decreased monocytic myeloid-derived suppressor cells (M-MDSCs) population in blood and spleen of mice. The in vitro assay demonstrated that Dioscin promoted M1 as well as inhibited M2 macrophages phenotype in LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model. Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC.

ETHNOPHARMACOLOGICAL RELEVANCE Dioscorea nipponica Makino as a Chinese folk medicine has been used for the treatment of chronic bronchitis, cough, and asthma. Several studies have established the antimetastatic potential of Dioscorea nipponica Makino extract. Dioscin is a major bioactive compound in Dioscorea nipponica Makino and has anti-tumor property in lung cancer cell lines. However, the preventive effect of dioscin against lung cancer and its key mechanism haven't been identified yet. AIM OF STUDY To identify the prevention effect of dioscin on lung cancer and explore its key mechanism based on network pharmacology and experimental validation. METHODS The potential targets of dioscin were obtained from the HERB database. The therapeutic targets of lung cancer were acquired from the GeneCards database. Protein-protein interaction network (PPI) was constructed in the STRING 11.0 database. The David database was used for enrichment analysis. Molecular Docking was finished by the AutoDock Vina. NSCLC cell lines and mouse lung cancer model were used to confirm the prevention effect of dioscin on lung cancer and its key mechanism. RESULTS 76 potential targets of dioscin were identified to be involved in lung cancer treatment, which refer to 512 biological processes, 47 molecular functions, 77 cellular components and 107 signal pathways. The molecular docking suggested that dioscin might bind to AKT1, Caspase3, TP53, C-JUN and IL-6. The DARTS indicated that dioscin could bind to AKT1. In vitro, dioscin could decrease proliferation, invasion and migration in A549 and PC-9 cells with the significant reduction in the expression of p-AKT, MMP2, and PCNA. In vivo, dioscin could reduce lung nodules, lung injury, and mortality in mouse lung cancer model with reducing the expression of p-AKT, MMP2, PCNA and increasing the expression of active-caspase3. CONCLUSION Dioscin could prevent lung cancer and its key target is AKT1 kinase, a center protein of PI3K/AKT signaling pathway.

Atherosclerosis (AS) is one of the major causes leading to mortality of dysfunctional cardiovascular events in the menopausal women, which has long-term deficiency of estrogen. At present, the primary treatment for postmenopausal AS is hormone replacement therapy (HRT). However, it can increase the risks of ovarian and uterine cancers with long-term therapy. So seeking for a phytoestrogen which can overcome the disadvantages of HRT is a great mission. Dioscin, a traditional Chinese medicine, extracted from the roots of dioscorea nipponica, has anti-inflammatory, anti-tumor and anti-apoptosis activities. Especially, it also has estrogenic activity. Thus, this study aims to investigate the effects of dioscin on postmenopausal AS. Currently, ovariectomy (OVX) is the accepted model for AS associated with estrogen deficiency, and it can mimic the cessation of ovarian function that occurs in postmenopausal women as well. We used the high fat diet and ovariectomy(HFD-OVX)model to induce postmenopausal AS in the low-density lipoprotein receptor- deficient (LDLR-/-) mice. (1) The levels of TG, TC, LDL-C, HDLC, MDA, GSH, MDA and GSH in serum of HFD-OVX induced LDLR-/- mice were measured by colorimetric assay. (2) The artery injury of HFD-OVX induced LDLR-/- mice was detected with Oil Red O staining. (3) The protein expressions of NOX4, P22phox, IκB, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, bcl-2, PGC-1α, ERα, ERβ in the arterial tissue of HFD-OVX induced LDLR-/- mice were detected by Western blot analysis. In vitro, the model of human aortic endothelial cells (HAECs) induced by oxidized low-density lipoprotein (ox-LDL) (150 μg /ml) was established, and the molecular mechanism of dioscin on atherosclerosis in postmenopausal women was investigated. (1) The levels of MDA, GSH, MDA and GSH in ox-LDL induced HAEC cells were measured by colorimetric assay. (2) Reactive Oxygen Species (ROS) of ox-LDL induced HAEC cells was detected by fluorescence staining. (3) The protein expressions of PGC-1α, ERα, ERβ, NOX4, P22phox, IκB, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, bcl-2 and LC3 in ox-LDL induced HAEC cells were detected by Western blot analysis. (4) The autophagy level of ox-LDL induced HAEC cells was measured by transmission electron microscopy. (5) The applications of si-RNA transfection were used to explore whether dioscin could activate PGC-1α/ERα pathway to inhibit postmenopausal atherosclerosis. In vivo, we found that dioscin decreased the level of TG, TC, LDL-C and increased the level of HDLC in serum of HFD-OVX induced LDLR-/- mice, and it has protective effects to maintain the lipid homeostasis; The Oil Red O staining study showed that dioscin could significantly inhibit the formation of atherosclerotic plaques in HFD-OVX-treated LDLR-/- mice; Dioscin decreased the levels of NOX4, P22phox, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, but increased the levels of HDL-C, GSH, SOD, PGC-1α, ERα, ERβ, IκB, Bcl-2 and elevated the autophagy level in arterial tissues of HFD-OVX induced LDLR-/- mice. It is particularly worth mentioning that the up-regulating effect of dioscin on ERα is stronger than ERβ in OVX treated mice. In vitro, the results of colorimetric assay showed that dioscin decreased the level of MDA and LDH, increased the level of SOD and GSH in ox-LDL-induced HAEC cells; Dioscin also suppressed the release of ROS in ox-LDL-induced HAEC cells by fluorescence staining; Dioscin decreased the levels of NOX4, P22phox, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, but increased the levels of PGC-1α, ERα, ERβ, IκB, Bcl-2 and the ratio of LC3-II/LC3-I in ox-LDL-induced HAEC cells; Dioscin significantly elevated the autophagy level of ox-LDL-induced HAEC cells by transmission electron microscopy analysis; In addition, by si-RNA transfection, we found that the inhibitory effects of dioscin on oxidative stress, inflammatory response and apoptosis might partly through PGC-1α/ERα pathway in ox-LDL induced HAEC cells. The data of dual-Luciferase reporter assay revealed that dioscin activated ERα at least partly through PGC-1α pathway. Dioscin significantly inhibited oxidative stress, inflammatory response, apoptosis and increased the level of autophagy in vivo and vitro. In addition, dioscin could regulate the balance of lipid metabolism. Moreover, we proved that the effects of dioscin attenuating postmenopausal atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis were partly dependent on PGC-1α/ERα pathway. Therefore, dioscin, as a phytoestrogen, might become a drug for the treatment of atherosclerosis in postmenopausal women.

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Paridis Rhizoma is a natural medicine with strong anti-tumor and anti-inflammatory activities. Our previous research have found that Fusarium sp. C39, an endophytic fungus isolated from Dioscorea nipponica which contains the similar chemical components, significantly increased the steroidal saponins content of Paridis Rhizoma by fermentation. In this study, the inhibitory effects of fermentated Paridis Rhizoma extract (PRE) on liver cancer cells (Hepal-6), cervical cancer cells (Hela), and lung cancer cells (A549) were determined to be stronger than that of the unfermented extract. For discovering the fermentation mechanism of PRE with Fusarium sp. C39, 36 components with obviously quantitative variations were screened out by UPLC-Q/TOF-MS and 53 key genes involved in the metabolic pathways of steroidal saponins were identified by transcriptome. On the basis of comprehensively analyzing information from the metabonomics and transcriptome, it can be speculated that the increase of spirostanol saponins and nuatigenin-type saponins enhanced the inhibitory effect of fermented PRE on cancer cell proliferation. Under the action of glycosidase, glycosyltransferase, oxidoreductases, and genes involved in sterol synthesis, strain C39 achieved the synthesis of diosgenin and the alteration of configurations, sugar chain and substituent of steroidal saponins. The research suggested a microbial transformation approach to increase the resource utilization and activity of Paris polyphylla.

The dried rhizome of Dioscorea nipponica Makino ("Chuanshanlong" in Chinese) is a medicinal herb with multiple major producing areas. The main objective of this study was the comparative profiling of Dioscoreae Nipponicae Rhizoma (DNR) from various geographical origins. A hypoxia/reoxygenation-induced H9c2 cell injury model was established, and the antimyocardial ischemia activity of DNR samples from different origins was detected using the cell counting kit-8 (CCK-8) method. The result showed that the antimyocardial ischemia potential of DNR samples from the Heilongjiang province was higher than that of the other studied samples. Subsequently, a plant metabolomics technique utilizing ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q TOF-MS) was used to determine the differences in DNR samples from various geographical origins. Forty compounds, including steroidal saponins, free fatty acids, and organic acids, were tentatively identified based on UPLC-Q TOF-MS fragmentation pathways and via comparison with available reference standards. Partial least squares discriminant analysis was performed to estimate the differences in DNR samples from different origins. Five compounds were significantly up-regulated and correlated with antimyocardial ischemia in DNR samples from Heilongjiang province. Molecular docking was used to discern the interactions of key markers with the active sites of the target protein. The findings signified that UPLC-Q TOF-MS metabolomics coupled with molecular docking is a powerful tool to rapidly identify the quality control characteristics of DNR samples and their products. The research provides a direction for the rational utilization of DNR.

Background：Cardiovascular disease is the leading cause of death in both developed and developing countries. Di'ao Xinxuekang (DAXXK) is a pure Chinese medicine herbal preparation refined from dioscin extracted from the roots of Dioscorea panthaica Prain et Burk and Diosorea nipponica Makino. Objective: To evaluate the application of DAXXK in Cardiovascular disease. Methods: We searched and summarized all the studies on DAXXK and Cardiovascular disease in pumend, Google, and CNKI. Results：Modern pharmacological studies have shown that DAXXK has pharmacological effects such as dilating blood vessels, lowering blood pressure and cardiac load, improving hemodynamics, lowering blood lipids and anti-platelet aggregation, and is widely used for the therapy of various kinds of cardiovascular diseases, including hypertension, atherosclerosis, coronary heart disease (CHD), angina pectoris (AP) and myocardial infarction. We provide an overview of the clinical efficacy, molecular mechanisms, safety and therapeutic potential of DAXXK in the treatment of cardiovascular disease, aiming to provide clues and evidence for clinical decision-making. Conclusion：DAXXK exerts cardiovascular protection by regulating a variety of cardiovascular disease-related signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE Epimedium brevicornu Maxim, Dioscorea nipponica Makino, and Salvia miltiorrhiza Bunge formula (EDS) are three traditional Chinese medicines commonly combined and used to treat osteoarthritis (OA). However, the mechanism of its therapeutic effect on OA is still unclear. AIM OF THE STUDY The aim of this study was to investigate the potential anti osteoarthritis mechanism of EDS in the treatment of OA rats' model by quantitative proteomics. MATERIALS AND METHODS A papain-induced rat OA model was established, and then EDS was intragastrically administered for 28 days. A label-free quantification proteomics was performed to evaluate the holistic efficacy of EDS against OA and identify the possible protein profiles mechanisms. The expression levels of critical changed proteins were validated by RT-qPCR and Western blotting. The effects of EDS were then assessed by evaluating pathologic changes in the affected knee joint and measuring pressure pain threshold, acoustic reflex threshold, angle of joint curvature. RESULTS Proteomics analysis showed that 62 proteins were significantly upregulated and 208 proteins were downregulated in OA group compared to control group. The changed proteins were involved in activation of humoral immunity response, complement cascade activation, leukocyte mediated immunity, acute inflammatory response, endocytosis regulation, and proteolysis regulation. The EDS treatment partially restored the protein profile changes. The protective effects of EDS on pathologic changes in OA rats' knee joint and pain threshold assessment were consisted with the proteomics results. CONCLUSIONS The results suggest that EDS exerted synergistic therapeutic efficacies to against OA through suppressing inflammation, modulating the immune system, relieving joint pain, and attenuating cartilage degradation.

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