Tripterygium wilfordii Hook F (TwHF)‐based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that TwHF is a potential source of novel anti‐RA drugs. However, accumulating studies have observed that TwHF‐based therapy induces multi‐organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of TwHF. Notably, our research group developed a “Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis” (No. T/CACM 1337‐2020) approved by the China Association of Chinese Medicine to standardize the clinical application of TwHF‐based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of TwHF‐based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of TwHF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. We hope that this review will improve the understanding of TwHF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.
Bimetallic materials hold promise for improving catalyst activity, yet little is known about the photocatalytic mechanism that these systems undergo during photocatalytic reaction that lead to efficient catalyst. Herein, we synthesized g‐C3N4 combined with PtNix, which shows much higher photocatalytic activity than that of pure g‐C3N4 and achieves the highest H2 evolution rate of 8456 μmol h−1 g−1 for 2.5 % PtNix/g‐C3N4. The excellent photocatalytic activity resulted from the enhanced charge‐separation efficiency compared to the pristine g‐C3N4, which was proved by surface photovoltage, photoluminescence, and transient photovoltage spectra. Electrochemical impedance spectroscopy in the dark further confirms the ability of charge transfer of 2.5 % PtNix/g‐C3N4 is superior to that of pure g‐C3N4. This effective separation efficiency gives rise to the observed excellent photocatalytic activity. This study not only provides us with an efficient catalyst for water splitting, but opens new avenues for designing and developing platinum‐based photocatalysts.
Objective: Investigate the active ingredients and underlying hypolipidemic mechanisms of Danhe granule (DHG). Methods: The lipid-lowering effect of DHG was evaluated in hyperlipidemic hamsters induced by a high-fat diet. The ingredients absorbed into the blood after oral administration of DHG in hamsters were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A systems pharmacology approach incorporating target prediction and network construction, gene ontology (GO) enrichment and pathway analysis was performed to predict the active compounds and map the compounds-targets-disease network. Real-time polymerase chain reaction (RT-PCR) and Western blot were utilized to analyze the mRNA and protein expression levels of predicted targets. Results: DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. Sixteen ingredients absorbed into blood after oral administration of DHG were identified as the possible components interacted with targets. Moreover, 65 potential targets were predicted after targets intersection and compounds-targets-disease network mapping. Then, compounds-targets-pathways network mapping revealed that six active compounds (emodin, naringenin, etc.) compounds could interact with 10 targets such as sterol regulatory element binding protein (SREBP) 1c, SREBP-2 and peroxisome proliferation-activated receptor (PPAR) a, regulate three lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, and further affect lipid metabolic processes including fatty acid biosynthesis, low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARa, liver X receptor alpha (LXRa),
Artesunate (ART) has been indicated as a candidate drug for hepatocellular carcinoma (HCC). Glucosylceramidase (GBA) is required for autophagic degradation. Whether ART regulates autophagic flux by targeting GBA in HCC remains to be defined. Herein, our data demonstrated that the dramatic overexpression of GBA was significantly associated with aggressive progression and short overall survival times in HCC. Subsequent experiments revealed an association between autophagic activity and GBA expression in clinical HCC samples, tumor tissues from a rat model of inflammation-induced HCC and an orthotopic mouse model, and human HCC cell lines. Interestingly, probe labeling identified GBA as an ART target, which was further verified by both a glutathione-S-transferase pulldown assay and surface plasmon resonance analysis. The elevated protein expression of LC3B, the increased numbers of GFP-LC3B puncta and double-membrane vacuoles, and the enhanced expression of SQSTM1/p62 indicated that the degradation of autophagosomes in HCC cells was inhibited by ART treatment. Both the in vitro and in vivo data revealed that autophagosome accumulation through targeting of GBA was responsible for the anti-HCC effects of ART. In summary, this preclinical study identified GBA as one of the direct targets of ART, which may have promising potential to inhibit lysosomal autophagy for HCC therapy.
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