Bioactive compounds from Polygonatum genus as anti-diabetic agents with future perspectives.

Diabetes mellitus (DM) is one of the most serious health problems worldwide. Species in the genus Polygonatum are traditional food and medicinal plants, which play an important role in controlling blood glucose. In this reveiw, we systematically summarized the traditional and modern applications of the genus Polygonatum in DM, focused on the material bases of polysaccharides, flavonoids and saponins. We highlighted their mechanisms of action in preventing obese diabetes, improving insulin resistance, promoting insulin secretion, regulating intestinal microecology, inhibiting advanced glycation end products (AGEs) accumulation, suppressing carbohydrate digestion and obsorption and modulating gluconeogenesis. Based on the safety and efficacy of this 'medicinal food' and its utility in the prevention and treatment of diabetes, we proposed a research and development program that includs diet design (supplementary food), medical nutrition therapy and new drugs, which could provide new pathways for the use of natural plants in prevention and treatment of DM.

Polygonatum sibiricum ameliorated cognitive impairment of naturally aging rats through BDNF-TrkB signaling pathway.

Cognitive dysfunction is high in the elderly population and seriously affects the quality of life. Brain-derived neurotrophic factor (BDNF) is one of the key neurotrophic proteins, and activation of BDNF-TrkB is considered an effective strategy to improve cognitive dysfunction during aging. In this study, administration of polygonatum sibiricum (PS) for 5 months effectively ameliorates the cognitive function, improving the Nissl body state in cortex and hippocampus in aging rats. In addition, PS can improve the synaptic structure and increase the number of synapses. Furthermore, PS reverses the reduction of synaptic plasticity-related proteins postsynaptic density protein 95 (PSD-95) and synaptophysin during aging and up-regulates the expression of BDNF-TrkB. In conclusion, PS improves cognitive dysfunction and enhances synaptic plasticity in naturally aged rats by regulating the BDNF-TrkB signaling pathway. PS has the potential to be developed as a novel and promising functional health food for the elderly. PRACTICAL APPLICATIONS: Polygonatum sibiricum (PS) is a traditional Chinese medicine, which has been included in the homologous plant of medicine and food. PS has been widely used to treat lung diseases, diabetes and antiaging in clinical. Studies have confirmed that PS can accelerate the repair and regeneration of damaged neurons, reverse the changes in synaptic structure, and improve the ability of learning and memory. Our study confirmed that PS significantly improved the cognitive function in aging rats. PS has great potential to be developed as a functional food for improving neurological function and anti-aging.

Effect and mechanisms of Polygonatum kingianum (polygonati rhizome) on wound healing in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic dermatopathy is one of the most serious and common complications of diabetes. It has been found that high glucose can lead to abnormal glycometabolism. The skin microenvironment pollution caused by the increase in glucose and the oxidative stress mediated by the deposition of advanced glycation end products can lead to invisible skin injury, and the interaction between them is the key factor that makes the skin wounds of diabetic rats difficult to heal. Therefore, the main task of promoting healing is to reduce blood glucose levels and relieve the deposition of advanced glycation end products. Polygonatum kingianum Collett & Hemsl (PK) of Asparagaceae is planted in Yunnan, China, and is used by the Bai, Hani and Wa nationalities as a traditional medicine for preventing and treating diabetes. AIM OF THE STUDY: To study the effects of PK extract on skin wound healing in diabetic rats and to explore the regulatory mechanism of PK on wound microenvironment pollution, the antioxidative stress signaling pathway and latent injury of wound skin tissue. METHODS: First, wounds were prepared after diabetic rats were given PK extract by gavage for 4 weeks, and then gavage was continued for 2 weeks to observe and calculate the wound healing rate. A scanning electron microscope was used to observe the pathomorphological changes in the skin tissue at the edge of the wound. Western blotting was used to detect protein expression. Immunohistochemistry was used to detect the expression of CD34, AGEs, bFGF and VEGF. The Nrf2/HO-1 signaling pathway in skin tissue was detected by fluorescence quantitative PCR. Serum biochemical indicators and inflammatory cytokine levels were detected by a kit. RESULTS: After PK treatment, the wound healing rate increased significantly (P < 0.001), the infiltration of inflammatory cells in skin tissue of DM lesion rats decreased, the number of new blood vessels increased, and the epidermis and dermis thickened. The content of glucose, AGEs, RAGE protein and RAGE mRNA in skin decreased significantly (P < 0.05, P < 0.01, P < 0.001), while the expression of Nrf2 mRNA, HO-1 mRNA, CD34, bFGF and VEGF increased significantly (P < 0.05, P < 0.01, P < 0.001). The levels of SOD, GSH, MMP-9 and MMP-2 in skin decreased (P < 0.05, P < 0.01, P < 0.001), but the level of TIMP-2 increased (P < 0.001). GSP, GHb and ICAM-1 in plasma decreased (P < 0.05, P < 0.01, P < 0.001), while T-AOC, SOD and FINS increased (P < 0.05, P < 0.01). The levels of MDA, TNF-, IL-6, IL-2 and IFN-γ in plasma and wound skin tissue decreased (P < 0.05, P < 0.01, P < 0.001). CONCLUSION: PK can reduce the infiltration of inflammatory cells and glucose content in the skin tissue at the edge of the wound, reduce inflammatory factors in skin and plasma, and increase angiogenesis, thus improving the wound healing rate. PK can alleviate the microenvironment pollution caused by AGEs and glucose metabolism disorder in diabetic rats and induce antioxidant activity through the Nrf 2/HO-1 signaling pathway, thus reducing oxidative damage and offsetting endogenous skin damage and hidden damage.

Immunological regulation of the active fraction from Polygonatum sibiricum F. Delaroche based on improvement of intestinal microflora and activation of RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum, known as "Huangjing" in Chinese traditional medicine, of which functions include invigorating Qi and nourishing Yin, tonifying spleen and kidney, which are considered to replenish energy, and strengthen immunity. However, both the active components and mechanism of the immune-enhancing effect of Polygonatum sibiricum have not been clarified. AIM OF THE STUDY: To evaluate the immunoregulation effects of PSE30 (Polygonatum sibiricum ethanol 30) and PSE75 (Polygonatum sibiricum ethanol 75). The gut microbial and activation of RAW264.7 cells were also evaluated for exploring the mechanism of PSE75. MATERIALS AND METHODS: Female ICR mice were randomly divided into different groups, which were pretreated with 0.9% saline, Yupingfeng granules, different dosage of PSE30 or PSE75. And the immunosuppressed mice model was constructed using cyclophosphamide. And the total duration of the experiment was 15 d. After that, the serum Immunoglobulins G (IgG) and Immunoglobulins M (IgM) antibody, regular blood testing, assessment of natural killer cell activity, and histological observation of spleen in immunosuppressed mice were measured to evaluate the immunoregulation effects of PSE30 and PSE75. Besides, effects of PSE75 on gut microbial were evaluated using 16s rRNA sequence. And the mRNA expression and cytokine secretion of RAW264.7 cell were evaluated to analyze the immunoregulation mechanism of PSE75. RESULTS: The content of serum IgG, IgM was significantly elevated by PSE75 (P＜0.05, P＜0.001). The NK cells killing activity in splenocytes against K562 cells induced by PSE30, and PSE75 was pronounced higher than that of the model group (P < 0.05). Both mRNA expression of Th1 molecular markers including interleukin (IL)-2, interferon (IFN)-γ, and signal transducers and activators of transcription (STAT) 4, and Th2 molecular markers including IL-4 in splenocytes were markedly enhanced by PSE30, and PSE75 (P < 0.05, P < 0.01, or P < 0.001). Besides, the result of 16s rRNA sequence indicated that PSE75 could recover the gut microbial community disturbed by cyclophosphamide. PSE75 could markedly promote the secretion of IL-6, IL-10, and IL-12 p40 from RAW264.7 cell (P＜0.01, or P＜0.001). CONCLUSIONS: PSE75 was proved to be a more promising immunomodulation agent, of which may enhance the immunity of immunosuppressed mice by improving gut microbial and activating macrophages. And PSE75 could be developed as a good immune booster in the future.

Carbohydrate regulation response to cold during rhizome bud dormancy release in Polygonatum kingianum.

BACKGROUND: The rhizome of Polygonatum kingianum Coll. et Hemsl (P. kingianum) is a crucial traditional Chinese medicine, but severe bud dormancy occurs during early rhizome development. Low temperature is a positive factor affecting dormancy release, whereas the variation in carbohydrates during dormancy release has not been investigated systematically. Therefore, the sugar content, related metabolic pathways and gene co-expression were analysed to elucidate the regulatory mechanism of carbohydrates during dormancy release in the P. kingianum rhizome bud. RESULTS: During dormancy transition, starch and sucrose (Suc) exhibited opposing trends in the P. kingianum rhizome bud, representing a critical indicator of dormancy release. Galactose (Gal) and raffinose (Raf) were increased in content and synthesis. Glucose (Glc), cellulose (Cel), mannose (Man), arabinose (Ara), rhamnose (Rha) and stachyose (Sta) showed various changes, indicating their different roles in breaking rhizome bud dormancy in P. kingianum. At the beginning of dormancy release, Glc metabolism may be dominated by anaerobic oxidation (glycolysis followed by ethanol fermentation). After entering the S3 stage, the tricarboxylic acid cycle (TCA) and pentose phosphate pathway (PPP) were may be more active possibly. In the gene co-expression network comprising carbohydrates and hormones, HYD1 was identified as a hub gene, and numerous interactions centred on STS/SUS were also observed, suggesting the essential role of brassinosteroids (BRs), Raf and Suc in the regulatory network. CONCLUSION: We revealed cold-responsive genes related to carbohydrate metabolism, suggesting regulatory mechanisms of sugar during dormancy release in the P. kingianum rhizome bud. Additionally, gene co-expression analysis revealed possible interactions between sugar and hormone signalling, providing new insight into the dormancy release mechanism in P. kingianum rhizome buds.

Blood-Enriching Effects and Immune-Regulation Mechanism of Steam-Processed Polygonatum Sibiricum Polysaccharide in Blood Deficiency Syndrome Mice.

Polygonatum sibiricum Red. has been used as a medicinal herb and nutritional food in traditional Chinese medicine for a long time. It must be processed prior to clinical use for safe and effective applications. However, the present studies mainly focused on crude Polygonatum sibiricum (PS). This study aimed to investigate the chemical properties, blood-enriching effects and mechanism of polysaccharide from the steam-processed Polygonatum sibiricum (SPS), which is a common form of PS in clinical applications. Instrumentation analyses and chemistry analyses revealed the structure of SPS polysaccharide (SPSP). A mice model of blood deficiency syndrome (BDS) was induced by acetylphenylhydrazine (APH) and cyclophosphamide (CTX). Blood routine test, spleen histopathological changes, serum cytokines, etc. were measured. The spleen transcriptome changes of BDS mice were detected by RNA sequencing (RNA-seq). The results showed that SPSP consists predominantly of Gal and GalA together with fewer amounts of Man, Glc, Ara, Rha and GlcN. It could significantly increase peripheral blood cells, restore the splenic trabecular structure, and reverse hematopoietic cytokines to normal levels. RNA-seq analysis showed that 122 differentially expressed genes (DEGs) were obtained after SPSP treatment. GO and KEGG analysis revealed that SPSP-regulated DEGs were mainly involved in hematopoiesis, immune regulation signaling pathways. The reliability of transcriptome profiling was validated by quantitative real-time PCR and Western blot, and the results indicated that the potential molecular mechanisms of the blood-enriching effects of SPSP might be associated with the regulating of JAK1-STAT1 pathway, and elevated the hematopoietic cytokines (EPO, G-CSF, TNF-α and IL-6). This work provides important information on the potential mechanisms of SPSP against BDS.

Transcriptomic responses to drought stress in Polygonatum kingianum tuber.

BACKGROUND: Polygonatum kingianum Coll. et Hemsl. is an important plant in Traditional Chinese Medicine. The extracts from its tubers are rich in polysaccharides and other metabolites such as saponins. It is a well-known concept that growing medicinal plants in semi-arid (or drought stress) increases their natural compounds concentrations. This study was conducted to explore the morpho-physiological responses of P. kingianum plants and transcriptomic signatures of P. kingianum tubers exposed to mild, moderate, and severe drought and rewatering. RESULTS: The stress effects on the morpho-physiological parameters were dependent on the intensity of the drought stress. The leaf area, relative water content, chlorophyll content, and shoot fresh weight decreased whereas electrolyte leakage increased with increase in drought stress intensity. A total of 53,081 unigenes were obtained; 59% of which were annotated. We observed that 1352 and 350 core genes were differentially expressed in drought and rewatering, respectively. Drought stress driven differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, starch and sucrose metabolism, and stilbenoid diarylheptanoid and gingerol biosynthesis, and carotenoid biosynthesis pathways. Pathways such as plant-pathogen interaction and galactose metabolism were differentially regulated between severe drought and rewatering. Drought reduced the expression of lignin, gingerol, and flavonoid biosynthesis related genes and rewatering recovered the tubers from stress by increasing the expression of the genes. Increased expression of carotenoid biosynthesis pathway related genes under drought suggested their important role in stress endurance. An increase in starch and sucrose biosynthesis was evident from transcriptomic changes under drought stress. Rewatering recovered the drought affected tubers as evident from the contrasting expression profiles of genes related to these pathways. P. kingianum tuber experiences an increased biosynthesis of sucrose, starch, and carotenoid under drought stress. Drought decreases the flavonoids, phenylpropanoids, gingerol, and lignin biosynthesis. These changes can be reversed by rewatering the P. kingianum plants. CONCLUSIONS: These results provide a transcriptome resource for P. kingianum and expands the knowledge on the effect of drought and rewatering on important pathways. This study also provides a large number of candidate genes that could be manipulated for drought stress tolerance and managing the polysaccharide and secondary metabolites' contents in P. kingianum.

Physiological and transcriptomic analyses to reveal underlying phenolic acid action in consecutive monoculture problem of Polygonatum odoratum.

BACKGROUND: The root rot of fragrant solomonseal (Polygonatum odoratum) has occurred frequently in the traditional P. odoratum cultivating areas in recent years, causing a heavy loss in yield and quality. The phenolic acids in soil, which are the exudates from the P. odoratum root, act as allelochemicals that contribute to the consecutive monoculture problem (CMP) of the medicinal plant. The aim of this study was to get a better understanding of P. odoratum CMP. RESULTS: The phenolic acid contents, the nutrient chemical contents, and the enzyme activities related to the soil nutrient metabolism in the first cropping (FC) soil and continuous cropping (CC) soil were determined, and the differentially expressed genes (DEGs) related to the regulation of the phenolic acids in roots were analyzed. The results showed that five low-molecule-weight phenolic acids were detected both in the CC soil and FC soil, but the phenolic acid contents in the CC soil were significantly higher than those in the FC soil except vanillic acid. The contents of the available nitrogen, available phosphorus, and available potassium in the CC soil were significantly decreased, and the activities of urease and sucrase in the CC soil were significantly decreased. The genomic analysis showed that the phenolic acid anabolism in P. odoratum in the CC soil was promoted. These results indicated that the phenolic acids were accumulated in the CC soil, the nutrient condition in the CC soil deteriorated, and the nitrogen metabolism and sugar catabolism of the CC soil were lowered. Meantime, the anabolism of phenolic acids was increased in the CC plant. CONCLUSIONS: The CC system promoted the phenolic acid anabolism in P. odoratum and made phenolic acids accumulate in the soil.

Polygonatum cyrtonema Hua polysaccharide exhibits anti-fatigue activity via regulating osteocalcin signaling.

In the present study, we explored the anti-fatigue activity and its potential mechanism of a purified Polygonatum cyrtonema polysaccharide (PCP) on mice using weight-loaded swimming test. Results showed that PCP remarkably prolonged the exhaustive swimming time of mice when compared with normal control group. Meanwhile, PCP decreased serum levels of lactic acid (LA), blood uric nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), and increased the contents of liver glycogen, muscle glycogen and muscle ATP. These results revealed that PCP had good anti-fatigue ability. The histomorphologic analysis showed that PCP increased the cross-section area of the muscle fibers. Furthermore, PCP significantly enhanced the protein levels of bone morphogenetic protein-2 (BMP-2), phosphor-Smad1, Runt-related transcription factor 2 (Runx2) and osteocalcin (OC) in skeleton. Similar variation was also observed in the expression of osteocalcin signaling mediators of phosphorylated cAMP-response element binding protein (p-CREB) and phosphorylated hormone-sensitive lipase (p-HSL) in skeletal muscle. These results suggested that PCP resisted fatigue possibly via regulating osteocalcin signaling.

Integrated transcriptome and microRNA profiles analysis reveals molecular mechanisms underlying the consecutive monoculture problem of Polygonatum odoratum.

Polygonatum odoratum is a historically traditional Chinese medicine plant. However, the consecutive monoculture problem (CMP) widespread in other Chinese medicine limiting their cultivation on a large scale. In this study, the physiological data showed the adverse effect of CMP on the growth of P. odoratum under the consecutive cropping (CC) compared with the first cropping (FC). Then the high-throughput sequencing of miRNA and mRNA libraries of leaves and roots from FC and CC P. odoratum plants identified 671 differentially expressed genes (DEGs) and 184 differentially expressed miRNAs and revealed that the DEGs and target genes of the miRNAs were mainly involved in starch and sucrose metabolism, phenylpropanoid and brassinosteroid biosynthesis. The KEGG analysis revealed that the DEGs between CC and FC roots were enriched in the plant-pathogen interaction pathway. This study provided the expression regulation of genes related to CMP of P. odoratum but also suggested that CMP may result in the serious damage of pathogens to roots and cause the slow growth in the consecutive cropping plants.

Metabolomics study of polysaccharide extracts from Polygonatum sibiricum in mice based on 1 H NMR technology.

BACKGROUND: Polygonatum sibiricum Liliaceae perennial herb, as a commonly used medicine and food homologous plant, has been widely used in clinical practice of Chinese medicine since ancient times, with a history of 2000 years. As the main active ingredient, P. sibiricum polysaccharides have important pharmacological effects in blood sugar reduction and antitumor, antioxidant and liver protection. RESULTS: Mouse models of P. sibiricum polysaccharides were used in combination with 1 H NMR to investigate the metabolic regulation mechanism in mouse tissue and blood. The metabolite maps of the control group and the drug group in the liver had significant changes. The main differential metabolites were glucose 6-phosphate, inositol, lactose, glutamylglycine, galactose, rhamnose, cis-aconitic acid and histidine, indicating that there was definite correlation between the metabolic detection based on 1 H NMR and the metabolic characteristics of P. sibiricum. The common differential metabolites obtained by overall metabolism analysis were 3-hydroxybutyric acid, d-ribose, adenosine phosphate, inositol, fructose 6-phosphate, histidine, aspartic acid and cis-aconitic acid. CONCLUSIONS: This work forms the basis for identification of metabolic states combined with metabolic pathways, which could be used as diagnostic and prognostic indicators, providing therapeutic targets for new diseases. © 2020 Society of Chemical Industry.

[Biosynthetic pathways of Polygonatum cyrtonema polysaccharide and diosgenin based on its transcriptomic data].

Polygonatum cyrtonema belongs to the plant family Liliaceae, and its dried rhizome is one of the sources of Chinese traditional medicine of Polygonati Rhizoma. It possesses the dual function as both medicine and food. Its main chemical components are polysaccharides and saponins. In order to understand the biosynthesis pathway of polysaccharides and diosgenin in P. cyrtonema, the corresponding transcriptomic data were obtained by extracting and sequencing the RNA of four parts of P. cyrtonema, namely, leaves, stems, rhizomes and roots. By adopting BGISEQ-500 sequencing platform, 42.03 Gb data were retrieved. Subsequently, the de novo assembly was carried out by Trinity software to obtain 137 233 transcripts, of which 68.13% of unigenes were annotated in seven databases including KEGG, GO, NR, NT, SwissProt, Pfam and KOG. Transcripts that may be involved in the biosynthesis of polysaccharides and diosgenin were analyzed by data mining. With help of qPCR, we validated expression data of four genes that were possibly involved in the biosynthesis of target metabolites. This experiment provides data for the study of biosynthetic pathways of P. cyrtonema secondary metabolites and the clarification of related structural gene functions.

Transcriptome analyses of Paris polyphylla var. chinensis, Ypsilandra thibetica, and Polygonatum kingianum characterize their steroidal saponin biosynthesis pathway.

Steroidal saponins, one of the most diverse groups of plant-derived natural products, elicit biological and pharmacological activities; however, the genes involved in their biosynthesis and the corresponding biosynthetic pathway in monocotyledon plants remain unclear. This study aimed to identify genes involved in the biosynthesis of steroidal saponins by performing a comparative analysis among transcriptomes of Paris polyphylla var. chinensis (PPC), Ypsilandra thibetica (YT), and Polygonatum kingianum (PK). De novo transcriptome assemblies generated 57,537, 140,420, and 151,773 unigenes from PPC, YT, and PK, respectively, of which 56.54, 47.81, and 44.30% were successfully annotated, respectively. Among the transcriptomes for PPC, YT, and PK, we identified 194, 169, and 131; 17, 14, and 26; and, 80, 122, and 113 unigenes corresponding to terpenoid backbone biosynthesis; sesquiterpenoid and triterpenoid biosynthesis; and, steroid biosynthesis pathways, respectively. These genes are putatively involved in the biosynthesis of cholesterol that is the primary precursor of steroidal saponins. Phylogenetic analyses indicated that lanosterol synthase may be exclusive to dicotyledon plant species, and the cytochrome P450 unigenes were closely related to clusters CYP90B1 and CYP734A1, which are UDP-glycosyltransferases unigenes homologous with the UGT73 family. Thus, unigenes of ß-glucosidase may be candidate genes for catalysis of later period modifications of the steroidal saponin skeleton. Our data provide evidence to support the hypothesis that monocotyledons biosynthesize steroidal saponins from cholesterol via the cycloartenol pathway.

The regulatory mechanism of chilling-induced dormancy transition from endo-dormancy to non-dormancy in Polygonatum kingianum Coll.et Hemsl rhizome bud.

KEY MESSAGE: We identified three dormant stages of Polygonatum kingianum and changes that occurred during dormancy transition in the following aspects including cell wall and hormones, as well as interaction among them. Polygonatum kingianum Coll.et Hemsl (P. kingianum) is an important traditional Chinese medicine, but the mechanism of its rhizome bud dormancy has not yet been studied systematically. In this study, three dormancy phases were induced under controlled conditions, and changes occurring during the transition were examined, focusing on phytohormones and the cell wall. As revealed by HPLC-MS (High Performance Liquid Chromatography-Mass Spectrometry) analysis, the endo- to non-dormancy transition was association with a reduced abscisic acid (ABA)/gibberellin (GA3) ratio, a decreased level of auxin (IAA) and an increased level of trans-zeatin (tZR). Transmission electron microscopy showed that plasmodesmata (PDs) and the cell wall of the bud underwent significant changes between endo- and eco-dormancy. A total of 95,462 differentially expressed genes (DEGs) were identified based on transcriptomics, and clustering and principal component analysis confirmed the different physiological statuses of the three types of bud samples. Changes in the abundance of transcripts associated with IAA, cytokinins (CTKs), GA, ABA, brassinolide (BR), jasmonic acid (JA), ethylene, salicylic acid (SA), PDs and cell wall-loosening factors were analysed during the bud dormancy transition in P. kingianum. Furthermore, nitrilase 4 (NIT4) and tryptophan synthase alpha chain (TSA1), which are related to IAA synthesis, were identified as hub genes of the co-expression network, and strong interactions between hormones and cell wall-related factors were observed. This research will provide a good model for chilling-treated rhizome bud dormancy in P. kingianum and cultivation of this plant.

Pretreatment of Huaiqihuang extractum protects against cisplatin-induced nephrotoxicity.

Cisplatin is a commonly used chemotherapeutic agent in the treatment of different types of malignant tumors, but nephrotoxicity limits its usage. Therefore, in this study, we aimed to determine the possible protective effect of Huaiqihuang (HQH) extractum, a kind of Chinese herbal complex that consists of Trametes robiniophila Murr., Lycium barbarum and Polygonatum sibiricum, against nephrotoxicity induced by cisplatin in mice. We found that pretreatment with HQH significantly attenuated the cisplatin-induced increase in blood urea nitrogen (BUN), interstitial congestion, acute renal tubular injury and tubular cell apoptosis and necroptosis. It was further shown that HQH administration reduced cisplatin-induced release and nuclear-cytoplasmic translocation of HMGB1 and inactivated its downstream signaling molecules, TLR4 and NFκB, in renal tubular cells; as a result, HQH repressed cisplatin-induced TNF-α production. As dexamethasone (Dex) exerts renoprotective effects in severe Acute kidney injury (AKI), we compared it with HQH and found that HQH showed similar renoprotective effects to dexamethasone via similar mechanisms. Considering the potential side effects of corticosteroids, reducing the effectiveness of treatment and shortening survival in solid tumor patients, we suggest administration of HQH as a potential adjuvant for cisplatin therapy in solid tumor patients to preserve renal function.

The genus Polygonatum: A review of ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Polygonatum (Asparagaceae) comprises 71 species distributed throughout the temperate Northern Hemisphere. The medicinal plants of Polygonatum have been traditionally used as tonics in China, India, Pakistan, Iran and Japan, and have been demonstrated to be highly effective in clinical practice for treating age-related diseases, diabetes, lung diseases, fatigue, feebleness and indigestion. AIM OF THE REVIEW: This paper aims to provide the links among traditional uses, chemical constituents, pharmacological effects and toxicity to support their therapeutic potential and uncover opportunities for future research. MATERIALS AND METHODS: The relevant information on the genus Polygonatum was gathered from scientific databases (Google Scholar, Web of Science, SciFinder, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, CNKI). Information was also obtained from online databases, books, Ph.D. dissertations and M.Sc. theses. The literature cited in this review dates from 1917 to June 2017. RESULTS: At least 37 species and 1 variety of Polygonatum plants have been used as traditional medicine and functional food. The major chemical constituents of Polygonatum plants are steroidal saponins, triterpenoid saponins, homoisoflavanones, polysaccharides and lectins. A putative biosynthetic pathway of steroidal saponins and triterpenoid saponins has been established based on the compounds isolated from Polygonatum plants. The crude extracts and certain pure compounds from Polygonatum plants have shown a wide range of pharmacological effects such as anti-aging, anti-diabetic, anti-fatigue, and anticancer effects. The rhizomes of Polygonatum plants have a low degree of toxicity after processing. CONCLUSIONS: Based on this review, some traditional uses of Polygonatum species have been confirmed by pharmacological studies, such as its anti-osteoporosis, neuroprotective, immunomodulatory, anti-diabetic and anti-fatigue effects. Most of the pharmacological effects of this genus can be attributed to its polysaccharides, saponins and lectins. However, to clarify the chemical differences that lead to the different traditional uses between "Huangjing" (derived from P. sibiricum, P. kingianum, P. cyrtonema) and "Yuzhu" (derived from P. odoratum), a systematic comparison of the small molecule compositions and polysaccharides of these four species is needed. In addition to these four species, other locally used medicinal Polygonatum species should be the subject of research, and the chemical and pharmacological relationships of these species should be investigated to expand the medicinal resources and standardize the use of Polygonatum species.

De Novo Assembly and Analysis of Polygonatum sibiricum Transcriptome and Identification of Genes Involved in Polysaccharide Biosynthesis.

Polygonatum sibiricum polysaccharides (PSPs) are used to improve immunity, alleviate dryness, promote the secretion of fluids, and quench thirst. However, the PSP biosynthetic pathway is largely unknown. Understanding the genetic background will help delineate that pathway at the molecular level so that researchers can develop better conservation strategies. After comparing the PSP contents among several different P. sibiricum germplasms, we selected two groups with the largest contrasts in contents and subjected them to HiSeq2500 transcriptome sequencing to identify the candidate genes involved in PSP biosynthesis. In all, 20 kinds of enzyme-encoding genes were related to PSP biosynthesis. The polysaccharide content was positively correlated with the expression patterns of ß-fructofuranosidase (sacA), fructokinase (scrK), UDP-glucose 4-epimerase (GALE), Mannose-1-phosphate guanylyltransferase (GMPP), and UDP-glucose 6-dehydrogenase (UGDH), but negatively correlated with the expression of Hexokinase (HK). Through qRT-PCR validation and comprehensive analysis, we determined that sacA, HK, and GMPP are key genes for enzymes within the PSP metabolic pathway in P. sibiricum. Our results provide a public transcriptome dataset for this species and an outline of pathways for the production of polysaccharides in medicinal plants. They also present more information about the PSP biosynthesis pathway at the molecular level in P. sibiricum and lay the foundation for subsequent research of gene functions.

Discrimination of Polygonatum species and identification of novel markers using (1) H NMR- and UPLC/Q-TOF MS-based metabolite profiling.

BACKGROUND: Rhizomes of Polygonatum species are commonly used as herbal supplements in Asia. They have different medicinal effects by species but have been misused and mixed owing to their similar taste and smell. Therefore accurate and reliable analytical methods to discriminate between Polygonatum species are required. RESULTS: In this study, global and targeted metabolite profiling using (1) H nuclear magnetic resonance ((1) H NMR) spectroscopy and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was applied to discriminate between different Polygonatum species. Partial least squares discriminant analysis (PLS-DA) models were used to classify and predict species of Polygonatum. Cross-validation derived from PLS-DA revealed good predictive accuracy. Polygonatum species were classified into unique patterns based on K-means clustering analysis. 4-Hydrobenzoic acid and trigonelline were identified as novel marker compounds and quantified accurately. CONCLUSION: The results demonstrate that metabolite profiling approaches coupled with chemometric analysis can be used to classify and discriminate between different species of various herbal medicines. © 2015 Society of Chemical Industry.

Molecular switch role of Akt in Polygonatum odoratum lectin-induced apoptosis and autophagy in human non-small cell lung cancer A549 cells.

Polygonatum odoratum lectin (POL), isolated from traditional Chinese medicine herb (Mill.) Druce, has drawn rising attention due to its wide biological activities. In the present study, anti-tumor effects, including apoptosis- and autophagy-inducing properties of POL, were determined by a series of cell biology methods such as MTT, cellular morphology observation, flow cytometry, immunoblotting. Herein, we found that POL could simultaneously induce apoptosis and autophagy in human non-small cell lung cancer A549 cells. POL initiated apoptosis through inhibiting Akt-NF-κB pathway, while POL triggered autophagy via suppressing Akt-mTOR pathway, suggesting the molecular switch role of Akt in regulating between POL-induced apoptosis and autophagy. Moreover, ROS was involved in POL-induced inhibition of Akt expression, and might therefore mediate both apoptosis and autophagy in A549 cells. In addition, POL displayed no significant cytotoxicity toward normal human embryonic lung fibroblast HELF cells. Due to the anti-tumor activities, POL might become a potent anti-cancer drug in future therapy, which might pave the way for exploring GNA-related lectins into effective drugs in cancer treatment.

[Correlations between wild Polygonatum odoratum quality and main ecological factors].

By the methods of stepwise regression, principal component analysis, and grey relational grade analysis, this paper studied the correlations between the effective components (polysaccharides and water- and alcohol-soluble substances) contents and antioxidant activity of wild Polygonatum odoratum in different places and the ecological factors. Among the test ecological factors, the mean air temperature in January and in July, mean annual precipitation, frost-free period, and soil pH and total potassium were the main factors affecting the effective component contents of P. odoratum, with a contribution rate of 99.0%. As compared with soil factors, climatic factors made more contribution to the effective component contents. Soil total potassium was the key factor controlling the effective component contents, mean annual precipitation was the main decision factor, and mean air temperature in January was the main limiting factor. The plant polysaccharides and water-soluble substance contents were the key factors affecting the antioxidant activity of P. odoratum, and the capability of P. odoratum in excavating DPPH free radical increased with increasing contents of polysaccharides and water-soluble substances.