Hypoglycemic activity of immature persimmon (Diospyros kaki Thunb.) extracts and its inhibition mechanism for α-amylase and α-glucosidase.

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.

Ultrasound-Based Drug Delivery System.

Cancer still represents a leading threat to human health worldwide. The effective usage of anti-cancer drugs can reduce patients' clinical symptoms and extend life-span survival time. Current anti-cancer strategies include chemotherapy, traditional Chinese medicine, biopharmaceuticals, and the latest targeted-therapy. However, due to the complexity and heterogeneity of tumor, serious side effects may result from the direct use of anti-cancer drugs. Besides, the current therapeutic strategies failed to effectively alleviate metastasized tumors. Recently, ultrasound-mediated nano-drug delivery system has become an increasingly important treatment strategy. Due to its abilities to enhance the efficacy and reduce toxic and side effects, it has become a research hotspot in the field of biomedicine. In this review, we introduced the latest research progress of the ultrasound-responsive nano-drug delivery systems, and the possible mechanisms of ultrasound acting on the carrier to change the structure or conformation, as well as to realize the controlled release. In addition, the progress in ultrasound responsive nano-drug delivery systems will also be briefly summarized.

Effects of modified Wenjing decoction on microcirculation in reproductive organs in rats with symptom patterns of cold coagulation and blood stasis.

OBJECTIVE: To investigate the relationship between symptom patterns of cold coagulation and blood stasis (CCBS) and microcirculation disturbance. In addition, we determined the efficacy of modified Wenjing decoction (WJD) for the treatment of CCBS. METHODS: CCBS was induced in rats with an ice-water bath treatment. The ovarian function, microvascular and circulatory status of reproductive organs, and function of local microvascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were evaluated. RESULTS: Ovarian dysfunction was observed in the rats with CCBS. It was characterized by the presence of an estrous cycle disorder and a decrease in reproductive hormone levels. Microvascular circulation disorders were associated with an imbalance in vasoconstriction, relaxation substances, nitric oxide, abnormal blood flow in whole blood, and decreased blood flow in the auricle and uterus. VECs were damaged, and VSMCs contracted and proliferated in ovarian and uterine tissues. CONCLUSION: Our findings suggest that the dysfunctional reproductive organs observed in gynecological CCBS may be closely related to the microcirculation disturbance of local tissues, microvascular contraction, and vascular remodeling. Modified WJD can be used to treat CCBS by improving microcirculation in reproductive organs.

Extravascular gelation shrinkage-derived internal stress enables tumor starvation therapy with suppressed metastasis and recurrence.

Despite the efficacy of current starvation therapies, they are often associated with some intrinsic drawbacks such as poor persistence, facile tumor metastasis and recurrence. Herein, we establish an extravascular gelation shrinkage-derived internal stress strategy for squeezing and narrowing blood vessels, occluding blood & nutrition supply, reducing vascular density, inducing hypoxia and apoptosis and eventually realizing starvation therapy of malignancies. To this end, a biocompatible composite hydrogel consisting of gold nanorods (GNRs) and thermal-sensitive hydrogel mixture was engineered, wherein GRNs can strengthen the structural property of hydrogel mixture and enable robust gelation shrinkage-induced internal stresses. Systematic experiments demonstrate that this starvation therapy can suppress the growths of PANC-1 pancreatic cancer and 4T1 breast cancer. More significantly, this starvation strategy can suppress tumor metastasis and tumor recurrence via reducing vascular density and blood supply and occluding tumor migration passages, which thus provides a promising avenue to comprehensive cancer therapy.

Molecular cloning and characterization of 4-hydroxyphenylpyruvate dioxygenase gene from Lactuca sativa.

Vitamin E has been found to be associated with an important antioxidant property in mammals and plants. In photosynthetic organisms, the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD; E.C. 1.13.11.27) plays an important role in the vitamin E biosynthetic pathway. The full-length cDNA encoding HPPD was isolated from Lactuca sativa L. by rapid amplification of cDNA ends (RACE). The cDNA, designated as LsHPPD, was 1743 base pairs (bp) long containing an open reading frame (ORF) of 1338 bp encoding a protein of 446 amino acids. Sequence analysis indicated that LsHPPD shared high identity with HPPD from Medicago truncatula L. Real-time fluorescent quantitative PCR (qPCR) analysis revealed that LsHPPD was preferentially expressed in mature leaves compared with other tissues and that the LsHPPD expression was sensitive to high light and drought stress treatments. Transient expression of LsHPPD via agroinfiltration resulted in 12-fold increase in LsHPPD mRNA expression level and 4-fold enhancement in α-tocopherol content compared with the negative control. A decrease in chlorophyll content and inhibition of photosystem II were observed during stress treatments and agroinfiltration.

Molecular cloning and characterization of Crmdr1, a novel MDR-type ABC transporter gene from Catharanthus roseus.

A novel gene encoding a MDR-like ABC transporter protein was cloned from Catharanthus roseus, a medicinal plant with more than 120 kinds of secondary metabolites, through rapid amplification of cDNA ends (RACE). This gene (named as Crmdr1; GenBank accession no.: DQ660356) had a total length of 4395 bp with an open reading frame of 3801 bp, and encoded a predicted polypeptide of 1266 amino acids with a molecular weight of 137.1 kDa. The CrMDR1 protein shared 59.8, 62.5, 60.0 and 58.2% identity with other MDR proteins isolated from Arabidopsis thaliana (AAD31576), Coptis japonica (CjMDR), Gossypium hirsutum (GhMDR) and Triticum aestivum (TaMDR) at amino acid level, respectively. Southern blot analysis showed that Crmdr1 was a low-copy gene. Expression pattern analysis revealed that Crmdr1 constitutively expressed in the root, stem and leaf, but with lower expression in leaf. The domains analysis showed that CrMDR1 protein possessed two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs) arranging in "TMD1-NBD1-TMD2-NBD2" direction, which is consistent with other MDR transporters. Within NBDs three characteristic motifs common to all ABC transporters, "Walker A", "Walker B" and C motif, were found. These results indicate that CrMDR1 is a MDR-like ABC transporter protein that may be involved in the transport and accumulation of secondary metabolites.