Anti-inflammatory Effects of Ganoderma lucidum Triterpenoid in Human Crohnʼs Disease Associated with Downregulation of NF-κB Signaling

Abstract

Background Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Current medications have potentially serious side effects. Hence there is increasing interest in alternative therapies. We previously demonstrated the anti-inflammatory effects of FAHF-2 in-vitro on PBMCs and mucosa from CD subjects. Here we investigated the anti-inflammatory effects of a bioactive compound isolated from Ganoderma lucidum (G. lucidum), a key herbal constituent of FAHF-2, in CD in vitro. Methods Triterpene ganoderic acid C1 (GAC1) was isolated from G. lucidum. Stimulated RAW 264.7 macrophages were treated with GAC1. Human peripheral blood mononuclear cells (PBMCs) and colonic biopsies were obtained from children with CD and cultured with or without GAC1. TNF-α and other pro-inflammatory cytokine levels were measured in the culture supernatant. NF-κB signaling was investigated in PBMCs and colonic mucosa treated with GAC1 by In-Cell Western and western blot analysis. Results GAC1 decreased TNF-α production by macrophages and PBMCs from CD subjects. GAC1 significantly decreased TNF-α, IFN-γ, and IL-17A production by inflamed colonic biopsies from CD subjects. These effects were due to down-regulation of the NF-κB signaling pathway. Conclusions GAC1 inhibited production of TNF-α and other pro-inflammatory cytokines by PBMCs and inflamed CD colonic mucosa due to blockage of NF-κB activation. GAC1 is a key beneficial constituent in G. lucidum and the FAHF-2 formula in suppressing the inflammatory cytokines found in CD and warrants clinical investigation for the treatment of CD.

The Flavonoid 7,4′-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts

“…C and D ) for cell viability testing and annexin V flow cytometry assay for testing cell apoptosis (Fig. E) as previously described (Liu et al ., ). 7,4′‐DHF and Dex were not cytotoxic, and neither affected HFL‐1 cell; 7,4′‐DHF did not induce apoptosis .…”

“…Annexin V apoptosis assays were performed using an Annexin V–FITC Apoptosis Detection Kit (BD Biosciences) according to the manufacturer's instructions and flow cytometry as previously described (Liu et al ., ). Annexin V binds to phosphatidylserine, which is translocated from the inner to the outer leaflet of the membrane during apoptosis.…”

“…Western blot analysis was performed as previously described (Liu et al ., ) using anti‐p‐STAT6 (rabbit, 1:1000), p‐IκBα (rabbit, 1:1000), p‐Akt (rabbit, 1:1000), HDAC2 (rabbit, 1:1000), p‐glucocorticoid receptor (GCR, Ser 211, rabbit, 1:1000), and GADPH (rabbit, 1:5000) (Cell Signaling Technology, Danvers, MA, USA). Bands in triplicate samples were analyzed using Image J software.…”

Ganoderma Lucidum Induced Acute Pancreatitis in The Elderly

“…There are some evidences claimed that G. lucidum increases glycogen synthesis and cholesterol homeostasis, decreases gluconeogenesis, TNF-α and other pro-inflammatory cytokines. G. lucidum can also inhibate pro-invasive gene replication 7,8,9 . Other than the diseases mentioned above, G. lucidum is also used to treat hepatopathy, chronic hepatitis, neurasthenia, insomnia, bronchitis, gastric ulcers, atherosclerosis, leukopenia, anorexia and cancer 3 .…”

B‐FAHF‐2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy

“…[35] Some major active compounds including alkaloids and triterpenoids from BF2 have been identified and found to inhibit IgE production[36], mast cell activation, [37] and inhibited of pro-inflammatory cytokines in allergy [38] and other inflammatory conditions. [39] We, therefore, hypothesized that combining BF2 and multiple PN/ TN OIT would be more beneficial then OIT alone. The objectives of this study were to first generate a murine model of concurrent PN and tree nut allergies for which there was no previous report and test our hypothesis in this model.…”