Pharmacokinetics, tissue distribution, plasma protein binding rate and excretion of sinoacutine following intravenous administration in female and male Sprague-Dawley rats.

Sinoacutine is a natural isoquinoline alkaloid isolated from traditional Chinese medicine Stephanina yunnanensis H. S. Lo. Our aim was to study the pharmacokinetic characteristics of sinoacutine, which is essential during the development of new drugs.In this study, an accurate, sensitive, and efficient liquid chromatography (HPLC) method was developed and applied to evaluate the pharmacokinetics, tissue distribution, plasma protein binding rate, and excretion after intravenous injection of sinoacutine in rats.The pharmacokinetic parameters of sinoacutine were accorded with a two-compartment model in rats, and the AUC0-t in female was greater than that in male. Sinoacutine could be detected in heart, liver, spleen, lung, kidney, and brain, and the content in liver and kidney was relatively high. Meanwhile, it had a high plasma protein binding rate of 79.16%. Excretion of sinoacutine through faeces and urine was low, and the average excretion rate was 9.96%. There were gender differences in blood drug concentration, tissue distribution, and excretion significantly (p < 0.05).In summary, this study lays a foundation for elucidating the pharmacokinetic rule of sinoacutine and the data can provide a reliable scientific resource for further research.

The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo.

Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy. Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved. Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels. Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1ß and TNF-α) by LPS-induced RAW264.7 macrophages (p < .01). Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

Sinoacutine inhibits inflammatory responses to attenuates acute lung injury by regulating NF-κB and JNK signaling pathways.

BACKGROUND: Stephania yunnanensis H. S. Lo is widely used as an antipyretic, analgesic and anti-inflammatory herbal medicine in SouthWest China. In this study, we investigated the anti-inflammatory activity and mechanism of sinoacutine (sino), one of the primary components extracted from this plant. METHODS: A RAW264.7 cell model was established using lipopolysaccharide (LPS) induced for estimation of cytokines in vitro, qPCR was used to estimate gene expression, western blot analysis was used to estimate protein level and investigate the regulation of NF- κB, JNK and MAPK signal pathway. In addition, an acute lung injury model was established to determine lung index and levels of influencing factors. RESULTS: Using the RAW264.7 model, we found that sino reduced levels of nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß and prostaglandin E2 (PGE2) but increased levels of IL-6. qPCR analysis revealed that sino (50, 25 µg/ml) inhibited gene expression of nitric oxide synthase (iNOS). western blot analysis showed that sino significantly inhibited protein levels of both iNOS and COX-2. Further signalling pathway analysis validated that sino also inhibited phosphorylation of p65 in the NF-κB and c-Jun NH2 terminal kinase (JNK) signalling pathways but promoted the phosphorylation of extracellular signal regulated kinase (ERK) and p38 in the MAPK signalling pathway. In addition, in a mouse model induced by LPS, we determined that sino reduced the lung index and the levels of myeloperoxidase (MPO), NO, IL-6 and TNF-α in lung tissues and bronchoalveolar lavage fluid (BALF) in acute lung injury (ALI). CONCLUSION: Taken together, our results demonstrate that sino is a promising drug to alleviate LPS-induced inflammatory reactions.