One-pot total syntheses of natural products containing a THP-ring backbone: (±)-centrolobine and (±)-civet cat secretion

A one-pot strategy is devised and applied to the total syntheses of natural products with a THP-ring backbone. A special feature of this one-pot synthesis is the recyclability of the indium complex byproduct generated from the indium-mediated allylation reaction for concurrent catalysis in subsequent steps. Centrolobine and civet cat secretion are synthesized via this new method in overall yields of 58% and 23%, respectively.     

In Vitro Tests for a Rapid Evaluation of Antidiabetic Potential of Plant Species Containing Caffeic Acid Derivatives: A Validation by Two Well-Known Antidiabetic Plants,Ocimum gratissimum L. Leaf and Musanga cecropioides R. Br. ex Tedlie (Mu) Stem Bark

Plant bioactive extracts represent a major resource for identifying drugs and adjuvant therapy for type 2 diabetes. To promote early screening of plants’ antidiabetic potential, we designed a four in vitro tests strategy to anticipate in vivo bioactivity. Two antidiabetic plants were studied: Ocimum gratissimum L. (Oc) leaf extract and Musanga cecropoides R. Br. ex Tedlie (Mu) stem bark extract. Chemical compositions were analyzed by LCMS and HPLC. Antidiabetic properties were measured based on (1) INS-1 cells for insulin secretion, (2) L6 myoblast cells for insulin sensitization (Glut-4 translocation), (3) L6 myoblast cells for protection against hydrogen peroxide (H₂O₂) oxidative stress (cell mortality), and (4) liver microsomial fraction for glucose-6-phosphastase activity (G6P). Oc extract increased insulin secretion and insulin sensitivity, whereas it decreased oxidative stress-induced cell mortality and G6P activity. Mu extract decreased insulin secretion and had no effect on insulin sensitivity or G6P activity, but it increased oxidative stress-induced cell mortality. Results were compared with NCRAE, an antidiabetic plant extract used as reference, previously characterized and reported with increased insulin secretion and insulin sensitivity, protection against oxidative stress, and decreased G6P activity. The proposed set of four in vitro tests combined with chemical analysis provided insight into the interest in rapid early screening of plant extract antidiabetic potential to anticipate pharmaco-toxicological in vivo effects.     

POTENTIATED EFFECT OF VAGAL STIMULATION AND HORMONAL AGENTS ON PANCREATIC EXOCRINE SECRETION IN DOGS

Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula andgastric fistula. Both in chronic and acute experiments the degenerated right cervical vagusnerve was stimulated by electrical shock and the endogenous secretin and CCK was releasedby means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocainewere infused to analyse the interrelationship of neurohormones in the pancreatic exocrinesecretion. The results were as follows. In chronic experiments the pancreatic secretory la-tency was shorter and volume larger than that in acute experiments induced by D. A. Thedifference is very significant (P<0.001). Both vagotomy and atropine significantly inhibitedpancreatic secretion induced by D. A. (P<0.01). Lidocaine infused into duodenum inhibitedpancreatic secretion induced by D. A. as well. When vagal stimulation was combined withD. A., either simultaneously or successively, the pancreatic secretion was increased morethan the additive sum obtained by separate     

The Effect of Simulated In Vitro Digestion on Biological Activity of Viburnum opulus Fruit Juices

In the present study, an in vitro digestion method has been used to assay the influence of the physiological conditions in the mouth, stomach, and intestine on the stability and activity in different cell models of the main phenolic compounds from Viburnum opulus fresh juice (FJ), phenolic-rich juice (PJ), and the bioavailable fractions (DFJ and DPJ). The data obtained indicate that the V. opulus samples achieved after in vitro digestion had an influence on cellular glucose and lipid metabolism. The bioavailable fraction of both digested juices stimulated glucose uptake and decreased lipid accumulation by L6 myoblasts and HepG2 hepatocytes. Both DFJ and DPJ reduced the secretion of inflammatory cytokines by 3T3-L1 adipocytes: interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Simultaneously, DFJ and DPJ enhanced oxidative stress in MIN6 cells and decreased glucose-stimulated insulin secretion (GSIS). UPLC–MS analysis revealed qualitative and quantitative changes in hydroxycinnamic acids. In particular, the content of chlorogenic acid decreased drastically; its content in the bioavailable fraction was almost 7 times and 30 times lower than in the FJ and PJ, respectively. Our results suggested that although the phenolic compounds of V. opulus juices undergo transformation during digestion, they are still potent antioxidant agents with biological activity.     

Studies on the MxiH Protein in T3SS Needles Using DNP‐Enhanced ssNMR Spectroscopy

Bacterial T3SS needles formed by the protein MxiH are studied using DNP‐enhanced ssNMR spectroscopy at 14.1 T (600 MHz). This technique provides spectra of good resolution, allowing us to draw conclusions about the protein dynamics. With the obtained signal enhancement, samples of limited quantity now get within reach of ssNMR studies.     

Effect of Aucubin-Containing Eye Drops on Tear Hyposecretion and Lacrimal Gland Damage Induced by Urban Particulate Matter in Rats

Exposure to particulate matter is a causative factor of dry eye disease. We aimed to investigate the beneficial effect of eye drops containing aucubin on dry eye disease induced by urban particulate matter (UPM). Dry eye was induced in male SD rats (6 weeks old) by topical exposure to UPM thrice a day for 5 d. Eye drops containing 0.1% aucubin or 0.5% aucubin were topically administered directly into the eye after UPM exposure for an additional 5 d. Tear secretion was evaluated using a phenol red thread tear test and corneal irregularity. The oxidative damage in the lacrimal gland was evaluated using TUNEL and immunohistochemical staining. The topical administration of aucubin significantly attenuated UPM-induced tear hyposecretion (control group: 9.25 ± 0.62 mm, UPM group: 4.55 ± 0.25 mm, 0.1% aucubin: 7.12 ± 0.58 mm, and 0.5% aucubin: 7.88 ± 0.75 mm) and corneal irregularity (control group: 0.00 ± 0.00, UPM group: 3.40 ± 0.29, 0.1% aucubin: 1.80 ± 0.27, and 0.5% aucubin: 1.15 ± 0.27). In addition, aucubin also reduced the UPM-induced apoptotic injury of lacrimal gland cells induced by oxidative stress through the increased expression of HMGB1 and RAGE. These findings indicate that the topical administration of aucubin eye drops showed a beneficial effect against UPM-induced abnormal ocular changes, such as tear hyposecretion and lacrimal gland damage. Therefore, our results reveal the pharmacological activities of aucubin in dry eye disease.