Polygonati Rhizoma with the homology of medicine and food: A review of ethnopharmacology, botany, phytochemistry, pharmacology and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizoma (PR), which contains rich national cultural connotations, is a traditional Chinese medicine with homology of medicine and food. It has been used for a long time as a tonic in China's multi-ethnic medical system, and is also used to treat diseases such as premature graying hair, deficiency of blood and essence, diabetes, hypertension, etc. Meanwhile, PR is often used as food in China, India, South Korea and other Asian countries, which can satisfy hunger and provide many health benefits. AIM OF THE REVIEW: This paper systematically reviewed the ethnopharmacology, botany, phytochemistry, pharmacology and related applications research of PR, and provided a reference for the comprehensive applications of PR, including basic research, product development and clinical applications. This paper also refined the national application characteristics of PR, such as rich plant resources, special chemical components and anti-hidden hungry, which laid a foundation for its high value and high connotation development in the future. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine. RESULTS: A comprehensive analysis of the above literature confirmed that PR has been used in the ethnic medicine system of Asian countries such as China for thousands of years. In this paper, 12 species including official species that can be used as PR are summarized, which provide rich plant resources for PR. The chemical components in PR are divided into nutritional components and active components. The former not only contains non-starch polysaccharides and fructo-oligosaccharides, which account for about 50% in PR and are recognized as high-quality diet in the world, but also contains inorganic elements and mineral elements. And a total of 199 kinds active ingredients, including saponins, flavonoids, alkaloids, etc., were sorted out by us. The above ingredients make PR have a special property of anti-hidden hunger. Studies have shown that PR has a wide range of pharmacological activities, such as immune regulation, blood glucose regulation, lipid-lowering, antioxidant, anti-tumor, antibacterial, etc. It has been widely used in medicine, food, cosmetics, gardens and other fields. CONCLUSIONS: PR, as a classic medicinal material of the same origin, is widely used in the traditional ethnic medicine system. It contains abundant potential plant resources, chemical components and pharmacological activities. This paper also suggests that PR with high application value in food industry, has the potential to become a high-quality coarse grain. Exploring the way of grain and industrialization of PR is beneficial to fully develop the economic value of PR.

Global attitudes on and the status of enteral nutrition therapy for pediatric inflammatory bowel disease.

Enteral nutrition (EN) is a diet-remission therapy for inflammatory bowel disease (IBD) that plays a more important role in children than adults. EN includes exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), and maintenance enteral nutrition (MEN). However, EEN remains an unstandardized treatment for pediatric IBD. The types and methods of EN differ around the world. The current study reviewed the EN literature on children with IBD. A total of 12 survey studies were identified that analyzed the current state of EN use, including clinical opinions, implementation methods, treatment course, EEN formula, IBD classification, progress, dietary reintroduction, and patient feedback. The findings revealed that EEN has a strong effect on mild to moderate Crohn's disease (CD). The usage rates of this treatment in different sites were ileum/colon (Paris classification L3) > ileum (L1) > upper digestive tract (L4) > colon (L2) > perianal disease (P) > ulcerative colitis (UC) > extraintestinal lesions. The polymeric formula was the most used EN formulation. New EN diets include a CD exclusion diet (CDED), a specific carbohydrate diet (SCD), and a CD treatment-with-eating (CD-TREAT) diet. Children with IBD responded similarly to EEN administered orally or using a feeding tube. Most guidelines recommended 6-8 weeks of EEN treatment to induce remission. Many clinicians preferred to combine drug medications during EEN and recommended that MEN accounts for at least 25-35% of daily caloric intake. EN remains an unstandardized therapy that requires teamwork across disciplines.

Effect of cyasterone on intestinal flora in a BRAFV600E-mutant mouse model of colorectal cancer.

BRAF V600E-mutated colorectal cancer (CRC) is very aggressive and responds poorly to standard treatment. In this study, BRAFV600E-mutant mice with CRC were treated with intragastric cyasterone, a compound commonly used in traditional Chinese herbal medicine, for 21 days. Microbial DNA was extracted from mouse intestinal contents for 16S ribosomal RNA gene amplicon sequencing and analyzed. Our results indicated that cyasterone enhanced the diversity of the gut microbiota. The abundance of beneficial bacteria, such as Prevotellaceae, Muribaculaceae, and Ruminococcaceae was significantly higher in cyasterone-treated mice than controls. The abundance of Erysipelotrichaceae, a family of bacteria that promotes inflammation in the gut, was significantly positively correlated with tumor weight. Cyasterone is a potential inhibitor of BRAFV600E-mutant CRC via its effects on intestinal flora.

Action Mechanism Underlying Improvement Effect of Fuzi Lizhong Decoction on Nonalcoholic Fatty Liver Disease: A Study Based on Network Pharmacology and Molecular Docking.

OBJECTIVE: This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. METHODS: The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. RESULTS: A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3'-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. CONCLUSIONS: This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.

Nicotinamide Mononucleotide Ameliorates Silica-Induced Lung Injury through the Nrf2-Regulated Glutathione Metabolism Pathway in Mice.

Nicotinamide mononucleotide (NMN) is a natural antioxidant approved as a nutritional supplement and food ingredient, but its protective role in silicosis characterized by oxidative damage remains unknown. In this study, we generated a silicosis model by intratracheal instillation of silica, and then performed histopathological, biochemical, and transcriptomic analysis to evaluate the role of NMN in silicosis. We found that NMN mitigated lung damage at 7 and 28 days, manifested as a decreasing coefficient of lung weight and histological changes, and alleviated oxidative damage by reducing levels of reactive oxygen species and increasing glutathione. Meanwhile, NMN treatment also reduced the recruitment of inflammatory cells and inflammatory infiltration in lung tissue. Transcriptomic analysis showed that NMN treatment mainly regulated immune response and glutathione metabolism pathways. Additionally, NMN upregulated the expression of antioxidant genes Gstm1, Gstm2, and Mgst1 by promoting the expression and nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Gene interaction analysis showed that Nrf2 interacted with Gstm1 and Mgst1 through Gtsm2. Promisingly, oxidative damage mediated by these genes occurred mainly in fibroblasts. In summary, NMN alleviates silica-induced oxidative stress and lung injury by regulating the endogenous glutathione metabolism pathways. This study reveals that NMN supplementation might be a promising strategy for mitigating oxidative stress and inflammation in silicosis.

Cryptotanshinone reverses the epithelial-mesenchymal transformation process and attenuates bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial pneumonia that causes pulmonary tissue damage and functional impairment. To investigate the effects of cryptotanshinone on pulmonary fibrosis, the expression of NIH/3T3, HPF, and rat primary pulmonary fibroblasts was measured and found to be inhibited by CPT in a time- and concentration-dependent manner, and the upregulation of α-SMA expression in NIH/3T3 and HPF cells, which had been stimulated by TGFß-1, was decreased after CPT administration. We observed that CPT could reverse the increase in α-SMA expression and vimentin and the decrease in E-cad expression in A549 cells, which had been induced by 5 ng/mL TGFß-1, indicating that CPT has inhibitory effects in the EMT process. A BLM-induced pulmonary fibrosis model was established in C57BL/6 mice. The lung coefficient and hydroxyproline content increased significantly in the BLM-induced group and were decreased in the CPT-treated group. The expression levels of collagen-I and α-SMA and the phosphorylation level of Stat3 were significantly increased, and CPT treatment decreased these levels. Furthermore, the results from the flow cytometry analysis indicated that, in lung tissues, the frequencies of MDSCs, macrophages, DCs and T cells were considerably increased in the BLM-induced group, while CPT treatment reduced these immunocyte populations.

Reduced thiamine binding is a novel mechanism for TPK deficiency disorder.

Thiamine pyrophosphokinase (TPK) converts thiamine (vitamin B1) into thiamine pyrophosphate (TPP), an essential cofactor for many important enzymes. TPK1 mutations lead to a rare disorder: episodic encephalopathy type thiamine metabolism dysfunction. Yet, the molecular mechanism of the disease is not entirely clear. Here we report an individual case of episodic encephalopathy, with familial history carrying a novel homozygous TPK1 mutation (p.L28S). The L28S mutation leads to reduced enzymatic activity, both in vitro and in vivo, without impairing thiamine binding and protein stability. Thiamine supplementation averted encephalopathic episodes and restored the patient's developmental progression. Biochemical characterization of reported TPK1 missense mutations suggested reduced thiamine binding as a new disease mechanism. Importantly, many disease mutants are directly or indirectly involved in thiamine binding. Thus, our study provided a novel rationale for thiamine supplementation, so far the major therapeutic intervention in TPK deficiency.

[The Extract from Punica Granatum (Pomegranate) Leaves Promotes Apoptosis and Impairs Metastasis in Prostate Cancer Cells].

OBJECTIVE: To investigate the effects of pomegranate leaves extract(PLE)on proliferation,apoptosis and metastasis of prostate cancer cells. METHODS: The proliferation of TRAMP-C1,DU145,PC3 prostate cancer cells treated with different concentrations of PLE (final mass concentrations were 12.5,25,50,100, 200 µg/mL,respectively) for different time (24,48,72 h) was detected by MTT assay. Colony formation assay was performed to verify the long-term effects of PLE on the proliferation of DU145 and PC3 cells.After being treated with PLE for 48 h,Hoechst-33258 staining was used to observe the changes in the nucleus,the cell apoptotic rate was detected by flow cytometry,and wound-healing migration assay was perform to test the change of migration. RESULTS: In comparison with the control group,PLE in the range of 12.5-200 µg/mL had a certain inhibitory effect on the proliferation of TRAMP-C1,DU145 and PC3 cells ( P<0.05).In the range of 6.25-100 µg/mL,the number of colony formation of DU145 and PC3 was significantly reduced( P<0.01).After PLE treated for 48 h, the apoptotic features of nuclear fragmentation and the formation apoptotic body was observed in PC3. With the increase of concentration,the apoptotic rate increased gradually ( P<0.05),and the ability of cells to migrate to the scratch area was significantly weaker than the control group ( P<0.01). CONCLUSION: PLE has effect on proliferation,apoptosis and metastasis of prostate cancer cells.

The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells.

Prostate cancer is a big threat to male for its poor prognosis and high mortality rate. Natural compounds are important resources of many anticancer drugs. Pomegranate is a kind of antioxidant-rich fruit and its peel and seed has potential anticancer activities. In this study, we aimed to investigate the effects of pomegranate peel extract (PoPx) on the apoptosis and metastasis of prostate cancer cells and the related mechanism. We found that PoPx showed growth inhibition on prostate cancer cells. Nuclei morphological and flow cytometer (FCM) analysis indicated that PoPx could induce prostate cancer apoptosis. Further investigation indicated that mitochondrial mediated intrinsic pathway is involved in the apoptosis. Exposure to PoPx led to loss of mitochondrial transmembrane potential (Δym), accumulation of reactive oxygen species (ROS). Western blot analysis showed that PoPx could increase the expression ratio of Bax/Bcl2 and activation of apoptosis executor caspase 3. Wound healing assay and transwell migration and invasion assay implied that PoPx has the potential to inhibit migration and invasion, two critical steps in prostate cancer metastasis. Downregulation of MMP2/MMP9 and upregulation of TIMP2 showed accordance with the inhibition of migration and invasion. In summary, the present data showed that PoPx could be a promising drug candidate to treat prostate cancer, showing us a better way to develop novel drugs from natural compounds.

Synthesis, characterization, and in vitro and in vivo evaluation of a novel pectin-adriamycin conjugate.

Adriamycin (ADM) has been widely used in the treatment of many types of solid malignant tumor. However, cardiotoxicity, multidrug resistance and a short half-life in vivo are significant problems that limit its clinical application. To resolve these problems, a novel pectin-adriamycin conjugate (PAC) was synthesized by attaching ADM to low-methoxylated pectin via an amide linkage. The ADM content and weight-average molecular weight (Mw) of PAC were greater than 25% (w/w) and 50,360 g/mol, respectively. PAC was highly stable in plasma, but 33.2% of ADM was released from PAC after incubation for 30 h with lysosomes derived from rat liver. PAC was distributed uniformly in the cytoplasm of most A549 cells and accumulated in the nucleus of a few A549 cells after incubation for 30 h. At concentrations equivalent to 0.125-1.000 microg of ADM/mL, PAC did not inhibit the growth of either A594 or B16 cells to the same extent as free ADM or a mixture of ADM and pectin. Interestingly, at all concentrations, PAC inhibited the growth of 2780cp cells in vitro significantly more effectively than ADM or the mixture of ADM and pectin. The anticancer effect of PAC in vivo was evaluated with C57BL/6 mice bearing pulmonary metastases of B16 cells. Compared with ADM and the mixture of ADM and pectin, PAC suppressed tumor growth significantly and prolonged the mean survival time of the B16-inoculated mice. PAC has great potential for development as a tumor targeting polymer-drug.

[Preparation and lymphatic targeting research of targeting antitumor drug: pectin-adriamycin conjugates].

Pectin, a polysaccharide extracted from the cell wall of plants, was used as the drug carrier to synthesize the pectin-adriamycin conjugates (P(A)n). The structure of the conjugates was confirmed by UV and IR. The degree of esterification (DE) of the pectin was assessed, and it was found that DE significantly influenced the carboxy group contents, inherent viscosity and galacturonic acid contents of the pectin. The results of drug release test in vitro showed that the conjugate was stable in normal saline, but was gradually enzymolyzed to release the adriamycin in blood plasma and in lymph nodes. The results of lymphatic targeting study of P(A), demonstrated that the modification of DE or drug coupling capacity of pectin significantly influenced the lymphatic targeting characteristics of P (A)n. The adriamycin concentration of lymph nodes was 208 times higher than that of plasma after local injection of the P(A)n, of which the adriamycin content was 27.9% and the pectin was deesterificated 120 minutes by the use of hypothermy alkaline deesterification method.