Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

[Chemical constituents of Psidium guajava and their antitumor and antifungal activities].

Twenty-six compounds, including sixteen meroterpenoids(1-16), a triterpenoid(17), four terpenoid derivatives(18-21), and five aromatic compounds(22-26), were isolated from the leaves of Psidium guajava. Their structures were identified by spectroscopic analyses including NMR and MS. Compounds 21-26 were obtained from plants of Psidium for the first time. Based on the structure,(R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate(24 a), an α-glucosidase inhibitor recently isolated from Paramignya trimera, should be revised as compound 24. Meroterpenoids 1-16 were evaluated for their antitumor and antifungal activities. Meroterpenoids psiguajadial D(4), guapsidial A(5), 4,5-diepipsidial A(7), guadial A(14), and guadial B(15) showed cytotoxicities against five human tumor cell lines(HL-60, A-549, SMMC-7721, MCF-7, and SW-480), among which 5 was the most effective with an IC_(50) of 3.21-9.94 µmol·L~(-1).

Novel dibenzofuran and biphenyl phytoalexins from Sorbus pohuashanensis suspension cell and their antimicrobial activities.

Two novel sulfur-containing dibenzofurans, sorbusins A (1) and B (2), two unprecedented biphenyl glycosides, 2'-hydroxyaucuparin 2'-O-ɑ-L-rhamnoside (3) and noraucuparin 5-O-ɑ-L-rhamnoside (4), and four known analogues (5-8), were isolated from Sorbus pohuashanensis suspension cell induced by yeast extract. Their structures were elucidated based on spectroscopic analyses and quantum calculation of 13C NMR data. Structurally, compound 1 possessed a rare naturally occurring benzothiazole moiety and represents the first example of thiazole fused dibenzofuran. A plausible biosynthetic pathway for the sulfur-containing dibenzofurans is proposed. These dibenzofuran and biphenyl phytoalexins were evaluated for their antimicrobial activities against pathogenic fungi and drug-resistant bacteria. Compound 7 exhibited significant antibacterial activity against methicinllin-resistant Staphylococcus aureus with an MIC value of 3.13 µg/mL.

Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor.

Chemotherapy-related fatigue (CRF) is increasingly being recognized as one of the severe symptoms in patients undergoing chemotherapy, which not only largely reduces the quality of life in patients, but also diminishes their physical and social function. At present, there is no effective drug for preventing and treating CRF. Ganoderic acid (GA), isolated from traditional Chinese medicine Ganoderma lucidum, has shown a variety of pharmacological activities such as anti-tumor, anti-inflammation, immunoregulation, etc. In this study, we investigated whether GA possessed anti-fatigue activity against CRF. CT26 tumor-bearing mice were treated with 5-fluorouracil (5-FU, 30 mg/kg) and GA (50 mg/kg) alone or in combination for 18 days. Peripheral and central fatigue-related behaviors, energy metabolism and inflammatory factors were assessed. We demonstrated that co-administration of GA ameliorated 5-FU-induced peripheral muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing glycogen content and ATP production, reducing lactic acid content and LDH activity, and inhibiting p-AMPK, IL-6 and TNF-α expression in skeletal muscle. Co-administration of GA also retarded the 5-FU-induced central fatigue-like behavior accompanied by down-regulating the expression of IL-6, iNOS and COX2 in the hippocampus through inhibiting TLR4/Myd88/NF-κB pathway. These results suggest that GA could attenuate 5-FU-induced peripheral and central fatigue in tumor-bearing mice, which provides evidence for GA as a potential drug for treatment of CRF in clinic.