• Anticancer activity
• Molecular simulation
• Natural products
• Structure-activity relationship
• Synthesis
• Triterpenoid

• Triterpenes/chemistry
• Triterpenes/pharmacology
• Humans
• Structure-Activity Relationship
• Antineoplastic Agents, Phytogenic/pharmacology
• Antineoplastic Agents, Phytogenic/chemistry
• Molecular Structure
• Neoplasms/drug therapy
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/chemical synthesis
• Animals
• Drug Screening Assays, Antitumor
• Cell Proliferation/drug effects

• The green walnut husks of Juglans mandshurica Maxim.
• antibacterial
• diarylheptanoid

• Juglans/chemistry
• Diarylheptanoids/chemistry
• Diarylheptanoids/pharmacology
• Diarylheptanoids/isolation & purification
• Staphylococcus aureus/drug effects
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/chemistry
• Anti-Bacterial Agents/isolation & purification
• Molecular Structure
• Escherichia coli/drug effects
• Microbial Sensitivity Tests
• Plant Extracts/chemistry
• Plant Extracts/pharmacology

Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers with high mortality rates worldwide. The main ingredients in Mu Ji Fang Granules (MJF) are alkaloids, flavonoids, and polysaccharides. MJF has been used in the clinical treatment of hepatitis, cirrhosis and HCC for more than 30 years. Few previous studies have focused on the mechanism of MJF on tumor immu-nology in the treatment of HCC.

To explore the mechanism of action of MJF on tumor immunology in the treatment of HCC.

The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight- Mass Spectrometry, and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis. Forty male mice were randomly divided into the Blank, Model, and MJF groups (1.8, 5.4, and 10.8 g/kg/d) following 7 d of oral administration. Average body weight gain, spleen and thymus indices were calculated, tumor tissues were stained with hematoxylin and eosin, and Interferon gamma (IFN-γ), Tumor necrosis factor α (TNF-α), Interleukin-2, aspartate aminotransferase, alanine aminotransferase, alpha-fetoprotein (AFP), Fas, and FasL were measured by Enzyme-linked Immunosorbent Assay. Relevant mRNA expression of Bax and Bcl2 was evaluated by Real Time Quantitative PCR (RT-qPCR) and protein expression of Transforming growth factor β1 (TGF-β1) and Mothers against decapentaplegic homolog (SMAD) 4 was assessed by Western blotting. The HepG2 cell line was treated with 10 mg/mL, 20 mg/mL, 30 mg/mL, 40 mg/mL of MJF, and another 3 groups were treated with TGF-β1 inhibitor (LY364947) and different doses of MJF. Relevant mRNA expression of TNF-α, IFN-γ, Bax and Bcl2 was evaluated by RT-qPCR and protein expression of TGF-β1, SMAD2, p-SMAD2, SMAD4, and SMAD7 was assessed by Western blotting.

It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumor-bearing mice, protected immune organs and liver function, reduced the HCC indicator AFP, affected immunity and apoptosis, and up-regulated the TGF-β1/SMAD signaling pathway, by increasing the relative expression of TGF-β1, SMAD2, p-SMAD2 and SMAD4 and decreasing SMAD7, reducing immune factors TNF-α and IFN-γ, decreasing apoptosis cytokines Fas, FasL and Bcl2/Bax, and inhibiting the effect of LY364947 in HepG2 cells.

MJF inhibits HCC by activating the TGF-β1/SMAD signaling pathway, and affecting immune and apoptotic cytokines, which may be due to MJF adjusting immune escape and apoptosis.

• Mu Ji Fang granules
• Hepatocellular carcinoma
• Transforming growth factor β1/Mothers against decapentaplegic homolog
• Immune escape
• H22 tumor-bearing mice
• HepG2 cells

• Juglans mandshurica Maximowicz
• Juglandaceae
• diarylheptanoid
• naphthoquinone

• Juglans mandshurica Maxim
• cytotoxic activities
• dammarane-type triterpenoid
• green walnut husks

• Antineoplastic Agents, Phytogenic/chemistry
• Juglans/chemistry
• Plant Extracts/chemistry
• Triterpenes/pharmacology
• Dammaranes

• Antioxidant activity
• Electronic beam irradiation
• Extraction
• Green walnut husk
• Structure

• Juglans regia
• Juglans regia polyphenol oxidase genes
• browning
• gene function analysis
• tobacco rattle virus
• virus-induced gene silencing

Juglans mandshurica Maxim., also known as “Manchurian walnut” (Chinese) and “Onigurumi” (Japanese), is a medicinal plant widely distributed in Western and Central Asia, especially in China. It has been traditionally used to treat cancer, gastric ulcers, diarrhea, dysentery, dermatosis, uterine prolapse, and leukopenia. To date, more than 400 constituents including quinones (e.g. naphthoquinones, anthraquinones, naphthalenones, tetralones), phenolics, flavonoids, triterpenoids, coumarins, lignans, phenylpropanoids, diarylheptanoids, and steroids, were isolated and structurally identified from different plant parts of J. mandshurica. Among them, quinones, phenolics, triterpenoids, and diarylheptanoids, as the major bioactive substances, have been extensively studied and displayed significant bioactivity. Previous studies have demonstrated that J. mandshurica and a few of its active components exhibit a wide range of pharmacologically important properties, such as antitumor, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetic, antiviral, antimicrobial, and anti-melanogenesis activities. However, many investigations on biological activities were mainly based on crude extracts of this plant, and the major bioactive ingredients responsible for these bioactivities have not been well identified. Further in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds, and more elaborate toxicity studies as well as clinical studies are needed to ensure safety and effectiveness of the plant for human use. Taken together, the present review will provide some specific useful suggestions guide to further investigations and applications of this plant in the preparation of medicines and functional foods.

• Juglans mandshurica
• antitumor activities
• pharmacology
• phytochemistry
• traditional uses

• Juglans mandshurica
• anti-inflammatory activity
• quinones