Transcriptome Analysis of Protection by Dendrobium nobile Alkaloids (DNLA) against Chronic Alcoholic Liver Injury in Mice

Abstract

Objective: To investigate the protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) against chronic alcoholic liver injury. C57BL/6J mice were fed with the Lieber–DeCarli alcohol diet to induce chronic alcoholic liver injury. DNLA (20 mg/kg/day) was gavaged along with the alcohol diet for 28 days. Liver injury was evaluated by serum enzymes. Triglyceride levels, histopathology, and transcriptome changes were examined by RNA-Seq and qPCR. DNLA decreased serum triglyceride levels in mice receiving alcohol. Hepatocyte degeneration and steatosis were ameliorated by DNLA, as evidenced by H&E and Oil-red O staining. DNLA brought the alcohol-induced aberrant gene expression pattern towards normal. Alcohol induced 787 differentially expressed genes (padj < 0.01). DNLA induced 280 differentially expressed genes to a much less extent. Ingenuity pathway analysis showed that DNLA ameliorated alcohol-induced oxidative stress and xenobiotic metabolism disruption. qPCR verified that DNLA alleviated over-activation of Cyp2a4, Cyp2b10, and Abcc4; attenuated oxidative stress (Hmox1, Gstm3, Nupr1), reduced the expression of Nrf2 genes (Nqo1, Gclc, Vldlr); and rescued some metabolic genes (Insig1, Xbp1, Socs3, Slc10a2). In conclusion, DNLA was effective against alcohol-induced fatty liver disease, and the protection may be attributed to alleviated oxidative stress and restored metabolism homeostasis, probably through modulating nuclear receptor CAR-, PXR-, and Nrf2-mediated gene expression pathways.

Quantitative analysis of six sesquiterpene glycosides from Dendrobium nobile Lindl. under different growth conditions by high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry in MRM mode

“…[2][3][4] Modern pharmacological studies have revealed that D. nobile exerts a variety of pharmacological effects, including immunomodulatory, neuroprotective, memory-improving, hypolipidemic, antitumor, blood pressure regulatory, antithrombotic, antioxidant, anticataract, hepatoprotective, cholagogue, antifatigue, bacteriostatic, and antiviral effects. [5][6][7][8][9][10][11] Significantly, sesquiterpene glycosides (SGs) from D. nobile have immunomodulatory, neuroprotective, and antitumor effects, and they can be used to treat diabetes and improve acute cerebral ischemia. [12][13][14] Studies have shown that dendronobiloside A, dendronobiloside B, dendroside A, dendroside G, and dendronobiloside D promote the proliferation of T and B lymphocytes.…”

“…The chemical constituents of D. nobile are complex, including alkaloids, sesquiterpenes, bibenzyls, phenanthrenes, phenylpropanoids, polysaccharides, etc 2–4 . Modern pharmacological studies have revealed that D. nobile exerts a variety of pharmacological effects, including immunomodulatory, neuroprotective, memory‐improving, hypolipidemic, antitumor, blood pressure regulatory, antithrombotic, antioxidant, anticataract, hepatoprotective, cholagogue, antifatigue, bacteriostatic, and antiviral effects 5–11 . Significantly, sesquiterpene glycosides (SGs) from D. nobile have immunomodulatory, neuroprotective, and antitumor effects, and they can be used to treat diabetes and improve acute cerebral ischemia 12–14 .…”