Five undescribed guanidine alkaloids from Plumbago zeylanica.

Five undescribed guanidine alkaloids, plumbagines HK (1-4) and plumbagoside E (5), as well as five known analogues (6-10) were isolated from the roots of Plumbago zeylanica. Their structures were established by extensive spectroscopic analyses and chemical methods. In addition, 1-10 were accessed their anti-inflammatory activities by measuring nitric oxide (NO) concentrations in LPS-induced RAW 264.7 cells. However, all compounds especially 1 and 3-5 could not inhibit the secretion of NO but significant increase the secretion of NO. The result reminded us that 1-10 may become potential novel immune potentiators.

Five glycosylated phenolic derivatives from the bark of Ilex rotunda Thunb. and their anti-inflammatory activities.

Five new glycosylated phenolic derivatives, rotundosides A-E (1-5), and three known glycosides (6-8) were isolated from the 95% alcohol extract of the bark of Ilex rotunda. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature data. All new compounds possessed a [5-O-(E)-caffeoyl]-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranosyl group. The anti-inflammatory properties of all isolated compounds were evaluated using a modified nitric oxide (NO) production in lipopolysaccharide (LPS)-induced leukemia cells in mouse macrophage (RAW264.7) method. Compound 8, dracunculifoside H, showed significant anti-inflammatory activity in vitro.

Recent discovery of tyrosinase inhibitors in traditional Chinese medicines and screening methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Tyrosinase, the key rate-limiting enzyme for melanogenesis, is one of the main targets for skin senescence and some pigmented skin diseases, such as albinism and melanoma. Tyrosinase inhibitors are capable of reducing melanin generation and deposition in the skin through blocking the reaction chain of formation. Thus, it has been used for anti-melanoma and showed the potential to be developed into novel skin whitening and spot removing products. With the trend of back-to-nature, natural tyrosinase inhibitors are receiving more and more attention. Traditional Chinese medicines (TCMs) as the promising source of novel chemotypes and pharmacophores, are huge treasures for the discovery of natural tyrosinase inhibitors characterized with green, safe, and highly efficient. AIM OF THIS REVIEW: This review aims to provide a systematic overview of natural tyrosinase inhibitors and a detailed summary of the types of TCMs from which they originate. In addition, this paper also highlights the screening methods developed for exploring tyrosinase inhibitors in recent years, compares the advantages and disadvantages of various methods under the guidance of different screening principles, and predicts their applications in the future. MATERIALS AND METHODS: Relevant literature have been obtained using the keywords "tyrosinase inhibitors", "traditional Chinese medicines", "whitening", and "screening" in scientific databases, such as "PubMed", "SciFinder", "Web of Science", "Elsevier", "China Knowledge Resource Integrated databases". Information was also collected from Chinese pharmacopoeia, Chinese herbal classics books, "Google Scholar", "Baidu Scholar", and other literature sources, etc. RESULTS: An overview about the tyrosinase inhibitors derived from TCMs since 2002 has been compiled via the above-mentioned sources. Up to now, 186 components, mainly belonging to flavonoids, lignans, terpenoids, Diels-Alder adducts, simple phenylpropanoids and stilbenes, from 61 kinds of TCMs have been reported to possess tyrosinase inhibitory activity, among which flavonoids are mainly focused on. Furthermore, on the basis of bioactive detection strategies, the screening methods for tyrosinase inhibitors have been classified into bioaffinity-based, intrinsic enzymatic-based, and computer-aided drug design (CADD). Precisely because screening approaches are essential for rapid identification of tyrosinase inhibitors from TCMs, the principles, advantages and disadvantages, and specific applications of each method are presented along with a comparison of applicability. CONCLUSIONS: The summary of TCMs-derived inhibitors gives a clue on the discovery of candidates with the property to whiten the skin. Meanwhile, the outlook of developed screening methods provides technical references for the efficient exploration of safer and more effective tyrosinase inhibitors from TCMs.

Annexin A2 promotes development of retinal neovascularization through PI3K/ AKT signaling pathway.

PURPOSE: Retinal Neovascularization (RNV) is a pathological characteristic of ocular diseases. Annexin A2 (ANXA2) plays important roles in RNV while the mechanism remains unclear. The study aimed to explore relationship between ANXA2 and PI3K/AKT signaling pathway in RNV. METHODS: We used human retinal vascular endothelial cells (HRECs) and oxygen-induced retinopathy (OIR) mice model to show ANXA2 can promote the development of RNV through PI3K/AKT signaling pathway. We divided HRECs into six groups by infecting lentivirus containing appropriate plasmid and adding corresponding solution. Assays showing ability of HRECs were performed in vitro. Mice were randomly divided into three groups and treated accordingly. RESULTS: Expression of ANXA2 and activity of PI3K/AKT signaling pathway in HRECs were detected. RNV and expression of ANXA2 in mice retinas were detected. Results showed that ANXA2 expression is positively related with RNV-forming ability of HRECs in vitro and development of RNV in vivo while low activity of PI3K/AKT signaling pathway could attenuate the role of ANXA2. CONCLUSIONS: We can make ANXA2 and PI3K/ AKT signaling pathway as a promising target for the regulation of pathological neovascularization of the retina, which also provides a novel idea for effective prevention and treatment of diseases related to RNV in future.

Inhibitory effect of miR­182­5p on retinal neovascularization by targeting angiogenin and BDNF.

Retinal neovascularization (RNV) is a type of serious vision­threating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, anti­VEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to anti­VEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brain­derived neurotrophic factor (BDNF) are implicated in angiogenesis, although their regulation and effects in RNV remain to be elucidated. microRNA (miRNA) is a type of small non­coding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNA­mediated modulation of ANG and BDNF was explored in an oxygen­induced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR­182­5p and upregulation of ANG and BDNF were found in vivo and in vitro. Overexpression of miR­182­5p suppressed the expression of ANG and BDNF significantly in HRECs under hypoxia. In addition, knockdown of ANG and BDNF by miR­182­5p transfection significantly improved hypoxia­induced HRECs dysfunctions, including enhancing cell viability, reducing cell migration and improved tube integrity. In conclusion, miRNA­dependent regulation on ANG and BDNF indicates a critical role in hypoxia­induced retinal microvascular response. miR­182­5p­based therapy can influence the expression of ANG and BDNF, which demonstrates the potential for treating RNV diseases.

Pilot-scale production of soybean oligopeptides and antioxidant and antihypertensive effects in vitro and in vivo.

Soybean oligopeptides (SOP) with low molecular weights were prepared by two-step enzymatic hydrolysis on a pilot-scale. Peptide and free amino acid contents of SOP were 82.5 ± 1.13 % and 3.7 ± 0.28 % respectively. The molecular weight distribution of SOP was mainly bellow 1,000 Da (85.4 %), 56.7 % of which were 140-500 Da. SOP showed strong stability to proteolytic digestion by pepsin and trypsin. The antioxidant activities and in vitro and in vivo antihypertensive effects of SOP were evaluated. Results showed that SOP exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging effect (IC50 = 4.5 ± 0.13 mg/mL), and significantly inhibited lipid peroxidation in linoleic acid oxidation system (IC50 = 1.2 ± 0.09 mg/mL). SOP had potent angiotensin I-converting enzyme inhibitory activity (IC50 = 1.1 ± 0.06 mg/mL), and antihypertensive effect in spontaneously hypertensive rats at a dose of 200 mg/kg. This study indicated that SOP could be a natural antioxidative or antihypertensive compound in the medicine and food industries.