Improved up-and-down procedure for acute toxicity measurement with reliable LD50 verified by typical toxic alkaloids and modified Karber method

Background Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20–42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim of this study was to test the reliability of iUDP to provide a reliable method for the acute toxicity measurement of valuable or minor amount compounds. Methods Oral median lethal dose (LD50) of nicotine, sinomenine hydrochloride and berberine hydrochloride were measured both by iUDP and modified Karber method (mKM). Results LD50 of the three alkaloids measured by iUDP with 23 mice were 32.71 ± 7.46, 453.54 ± 104.59, 2954.93 ± 794.88 mg/kg, respectively. LD50 of the three alkaloids measured by mKM with 240 mice were 22.99 ± 3.01, 456.56 ± 53.38, 2825.53 ± 1212.92 mg/kg, respectively. The average time consumed by the two methods were 22 days and 14 days respectively. Total grams of the alkaloids used by the two methods were 0.0082 and 0.0673 (nicotine), 0.114 and 1.24 (sinomenine hydrochloride), 1.9 and 12.7 (berberine hydrochloride). Conclusion iUDP could replace mKM to detect acute toxicity of substances with comparable and reliable result. And it is suitable for valuable or minor amount substances.

Sinomenine Hydrochloride Ameliorates Fish Foodborne Enteritis via α7nAchR-Mediated Anti-Inflammatory Effect Whilst Altering Microbiota Composition

Foodborne intestinal inflammation is a major health and welfare issue in aquaculture. To prevent enteritis, various additives have been incorporated into the fish diet. Considering anti-inflammatory immune regulation, an effective natural compound could potentially treat or prevent intestinal inflammation. Our previous study has revealed galantamine’s effect on soybean induced enteritis (SBMIE) and has highlighted the possible role of the cholinergic anti-inflammatory pathway in the fish gut. To further activate the intestinal cholinergic related anti-inflammatory function, α7nAchR signaling was considered. In this study, sinomenine, a typical agonist of α7nAChR in mammals, was tested to treat fish foodborne enteritis via its potential anti-inflammation effect using the zebrafish foodborne enteritis model. After sinomenine’s dietary inclusion, results suggested that there was an alleviation of intestinal inflammation at a pathological level. This outcome was demonstrated through the improved morphology of intestinal villi. At a molecular level, SN suppressed inflammatory cytokines’ expression (especially for tnf-α) and upregulated anti-inflammation-related functions (indicated by expression of il-10, il-22, and foxp3a). To systematically understand sinomenine’s intestinal effect on SBMIE, transcriptomic analysis was done on the SBMIE adult fish model. DEGs (sinomenine vs soybean meal groups) were enriched in GO terms related to the negative regulation of lymphocyte/leukocyte activation and alpha-beta T cell proliferation, as well as the regulation of lymphocyte migration. The KEGG pathways for glycolysis and insulin signaling indicated metabolic adjustments of α7nAchR mediated anti-inflammatory effect. To demonstrate the immune cells’ response, in the SBMIE larva model, inflammatory gatherings of neutrophils, macrophages, and lymphocytes caused by soybean meal could be relieved significantly with the inclusion of sinomenine. This was consistent within the sinomenine group as CD4+ or Foxp3+ lymphocytes were found with a higher proportion at the base of mucosal folds, which may suggest the Treg population. Echoing, the sinomenine group’s 16s sequencing result, there were fewer enteritis-related TM7, Sphingomonas and Shigella, but more Cetobacterium, which were related to glucose metabolism. Our findings indicate that sinomenine hydrochloride could be important in the prevention of fish foodborne enteritis at both immune and microbiota levels.

Sinomenine hydrochloride injection for knee osteoarthritis

Review question / Objective: At present, many clinical studies have been reported on the treatment of KOA by injecting sinomenine hydrochloride into the knee cavity. However, no systematic evaluation has been published on this issue, and it is not clear whether sinomenine hydrochloride injection is effective and safe in the treatment of KOA.Therefore, it is important to conduct systematic evaluation to obtain relatively convincing conclusions as to whether sinomenine hydrochloride injection can be a good choice as a complementary and alternative drug (CAM) for KOA. Condition being studied: The RCTs are eligible, whether or not the blind method is specifically described. There are no restrictions on languages. Moreover, systemic evaluation, review literature and the full article cannot be obtained will be excluded.

Improved Up-and-Down Procedure for Acute Toxicity Measurement With Reliable LD50 Verified by Typical Toxic Alkaloids and Modified Karber Method

Background: Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20 - 42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim of this study was to test the reliability of iUDP to provide a reliable method for the acute toxicity measurement of valuable or minor amount compounds. Methods: Oral median lethal dosage (LD50) of nicotine, sinomenine hydrochloride and berberine hydrochloride were measured both by iUDP and modified Karber method (mKM). Results: LD50 of the three alkaloids measured by iUDP with 23 mice were 32.71 ± 7.46, 453.54 ± 104.59, 2954.93 ± 794.88 mg/kg, respectively. LD50 of the three alkaloids measured by mKM with 240 mice were 22.99 ± 3.01, 456.56 ± 53.38, 2825.53 ± 1212.92 mg/kg, respectively. The average time consumed by the two methods were 22 days and 14 days respectively. Total grams of the alkaloids used by the two methods were 0.0082 and 0.0673 (nicotine), 0.114 and 1.24 (sinomenine hydrochloride), 1.9 and 12.7 (berberine hydrochloride). Conclusion: iUDP could replace mKM to detect acute toxicity of substances with comparable and reliable result. And it was suitable for valuable or minor amount substances.