An aberrant metabolic flow toward early shunt products in the granaticin biosynthetic machinery of Streptomyces vietnamensis GIMV4.0001.

A systematic study of the secondary metabolites of the wild granaticin-producing strain Streptomyces vietnamensis GIMV4.0001 led to the isolation of six known early shunt products related to actinorhodin, SEK34 (3), SEK34b (4), mutactin (5), dehydromutactin (7), EM18 (8) and GTRI-02 (9). While the other shunt products were minor or trace products, the production ratio of SEK34 (3) and SEK34b (4) to granaticins was strikingly high. Nearly 64% of the intermediate with the first ring closed went to the SEK34/SEK34b aberrant pathway. The high level of the aberrant metabolic flow toward the early shunt products SEK34 and SEK34b indicated that the second ring closure of the granaticin (1) biosynthesis is a key limiting step in the granaticin biosynthetic machinery of S. vietnamensis GIMV4.0001.

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3⁻5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (Cmax) at around 2 h, with an elimination half-life time (t1/2) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD50) of TTX pellets was 517.43 µg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 µg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection.

κ-Carrageenan/locust bean gum as hard capsule gelling agents.

A novel gelling agent, comprising blended κ-carrageenan (κ-C), a seaweed polysaccharide and locust bean gum (LBG), was used to prepare hard capsules. The distinct synergism between κ-C and LBG were verified by the textural profile analysis (TPA), FTIR and rheological measurement. Afterwards, films and hard capsules were prepared with the optimized LBG/κ-C blend gel. And the mechanical properties and morphology of films and hard capsules were analyzed by tensile testing and SEM, respectively. The results showed that the LBG/κ-C at 1:3 ratio could serve as an excellent gelling agent, which endowed hard capsule with the promoted mechanical properties, homogenous and smooth surface morphology. This work suggests that a novel blended LBG/κ-C gelling agent successfully prepared for hard capsules with improving physicochemical properties.