ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai". AIM OF THE STUDY: This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments. MATERIALS AND METHODS: First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylin & eosin (H&E) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration. RESULTS: Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P < 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment. CONCLUSION: HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways.
Subject(s)
Asthma/chemically induced , Asthma/drug therapy , Medicine, Traditional , Animals , Asian People , Databases, Factual , Dexamethasone/therapeutic use , Female , Humans , Mice , Mice, Inbred BALB C , Ovalbumin/toxicity , Random Allocation , Reproducibility of ResultsABSTRACT
<p><b>OBJECTIVE</b>To study the effect of several factors on the quantity of hypericin in H. perforatum callus.</p><p><b>METHOD</b>High efficiency liquid phase chromatography and plant tissue culture were applied.</p><p><b>RESULT AND CONCLUSION</b>When the ratio of nitro-nitrogen to amina-nitrogen is 3:1, the callus biomass is 1.6-fold and the synthetic mass of hypericin rises. 0.1-0.20 mg x L(-1) mannose improves the content of total hypericin. The addition of PVP or PVPP can promote improvement of the growth and biosynthesis of callus.</p>
Subject(s)
Culture Media , Hypericum , Metabolism , Mannose , Pharmacology , Nitrogen , Pharmacology , Perylene , Metabolism , Plants, Medicinal , Metabolism , Povidone , Pharmacology , Tissue Culture TechniquesABSTRACT
Artemisinin, a new and a very potent antimalarial drug, is produced by the Chinese medicinal herb Artemisia annua L. It is a sesquiterpene lactone with an endoperoxide bridge and is active against chloroquine resistant forms of Plasmodium falciparum. The relatively low yield (0.01% - 0.6%) of artemisinin in A. annua is a serious limitation to the commercialization of the drug. Therefore, a through understanding of the biosynthetic pathway and the characterization of the involved enzymes are important for the biology production of artemisinin. This review is focused on the recent progress in the molecular regulation of artemisinin biosynthesis from the following aspects: the biosynthetic pathway of artemisinin, the key enzymes involved in artemisinin biosynthesis, and the molecular regulation of artemisinin biosynthesis. The biosynthetic pathway of artemisinin belongs to the isoprenoid metabolite pathway, the key enzymes involved in the biosynthesis of artemisinin include: 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), farnesyl diphosphate synthase (FDPS), and amorpha-4, 11-diene synthase, of which amorpha-4, 11-diene synthase catalyzes the cyclisation of the ubiquitous precursor farnesyl diphosphate to the highly specific olefinic sesquiter-pene skeletons and has been postulated as the regulatory step in the biosynthesis of artemisinin. Recently the gene encoding of the amorpha-4, 11-diene synthase has been cloned and the functional expressions have been studied by several research teams, therefore, the breakthroughs in production of artemisinin could hopefully be achieved by metabolic engineering of the plant, in particular, by over-expressing enzyme(s) catalyzing the rate limiting step(s) of artemisinin biosynthesis or by inhibiting the enzyme(s) of other pathway competing for its precursors. Besides, the effects of the heterogenesis isoprenoid pathway related genes on artemisinin biosynthesis of the transformed plants were also discussed.