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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2019 · IF 4.527

Natural harmine negatively regulates the developmental signaling network of Drosophila melanogaster (Drosophilidae: Diptera) in vivo

Gaofeng Cui,Haiqi Yuan,Zhiyan Jiang,Jing Zhang,Zhipeng Sun,Guohua Zhong

The widely distributed β-carboline alkaloids exhibit promising psychopharmacological and biochemical effects. Harmine, a natural β-carboline, can inhibit insect growth and development with unclear mechanisms. In this study, harmine (at 0-200 mg/L) showed a dose-dependent inhibitory effect on the pupal weight, length, height, pupation rate and eclosion rate of fruit flies Drosophila melanogaster , which was similar to the inhibition induced by the well-known botanical insect growth regulator azadirachtin . Moreover, the expression levels of major regulators from the developmental signaling network were down-regulated during the pupal stage except Numb , Fringe , Yorkie and Pten . The Notch, Wnt, Hedgehog and TGF-β pathways mainly played vital roles in coping with harmine exposure in pupae stage, while the Hippo, Hedgehog and TGF-β elements were involved in the sex differences. Notch , Hippo , Hedgehog , Dpp and Armadillo were proved to be suppressed in the developmental inhibition with fly mutants, while Numb and Punt were increased by harmine. In conclusion, harmine significantly inhibited the development of Drosophila by negatively affecting their developmental signaling network during different stages. Our results establish a preliminary understanding of the developmental signaling network subjected to botanical component-induced growth inhibition and lay the groundwork for further application.

CAS / MDL: 442-51-3
研究领域: 昆虫学 · 分子生物学 · 发育生物学
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

Weierning, a Chinese patent medicine, improves chronic atrophic gastritis with intestinal metaplasia

Liping Han,Ting Li,Yingying Wang,Weizi Lai,Hengpu Zhou,Zhuangwei Niu,Jie Su,Guiyuan Lv,Guangji Zhang,Jianli Gao,Jianbo Huang,Zhaohuan Lou

Ethnopharmacological relevance Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled. Aim of the study The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism. Methods The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin , pepsinogen , and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6 , IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy , respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining. Results WEN could dose-dependently lower the serum level of IL-1β and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2 , and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG. Conclusion This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways’ activation.

CAS / MDL: 54-21-7
研究领域: 药理学 · 胃肠病学 · 中医
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