Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.

In recent decades, natural compounds derived from herbal medicine or dietary sources have played important roles in prevention and treatment of various diseases and have attracted more and more attention. Curcumin, extracted from the Curcumae Longae Rhizoma and widely used as food spice and coloring agent, has been proven to possess high pharmacological value. However, the pharmacological application of curcumin is limited due to its poor systemic bioavailability. As a major active metabolite of curcumin, tetrahydrocurcumin (THC) has higher bioavailability and stability than curcumin. Increasing evidence confirmed that THC had a wide range of biological activities and significant treatment effects on diseases. In this paper, we reviewed the research progress on the biological activities and therapeutic potential of THC on different diseases such as neurological disorders, metabolic syndromes, cancers, and inflammatory diseases. The extensive pharmacological effects of THC involve the modulation of various signaling transduction pathways including MAPK, JAK/STAT, NF-κB, Nrf2, PI3K/Akt/mTOR, AMPK, Wnt/β-catenin. In addition, the pharmacokinetics, drug combination and toxicology of THC were discussed, thus providing scientific basis for the safe application of THC and the development of its dietary supplements and drugs.

Uncontrolled hyperuricemia contributes to chronic kidney disease, characterized by renal inflammatory cell infiltration and tubulointerstitial fibrosis, eventually leading to renal failure. In addition to liver and kidney, the intestine tract plays a vital role in the development and progression of hyperuricemia and hyperuricemic nephropathy (HN) through various mechanisms. The conventional therapeutic strategy for HN is uric acid-lowering therapy (ULT) and renal protection; however, unsatisfactory results are often obtained in clinical practice. Growing evidence has demonstrated that traditional Chinese medicines (TCMs) achieve an anti-HN effect by modulating multiple targets and approaches with fewer side effects. Therefore, this paper reviews the pathogenesis of HN, including the role of soluble and insoluble urates in kidney and intestine, and the role of intestinal tract in the progression of HN. Meanwhile, the recent advancements in TCMs for the treatment of HN are summarized and analyzed, with a focus on their modulation of intestinal flora and metabolites, urate-related transporters, immuno-inflammation and barrier function in the intestines. Notably, for the first time, we propose the perspective that TCMs treat HN through a dual-regulatory effect on the intestines and kidneys. Additionally, the problems existing in current research and the feasible research strategies combined with emerging technologies such as fermentation and nanotechnology are discussed, thus providing novel ideas for HN management.

Sepsis (defined as sepsis 3.0) is a life-threatening organ dysfunction caused by a dysregulated host response to a variety of pathogenic microorganisms. Characterized by high morbidity and mortality, sepsis has become a global public health problem. However, there is a lack of appropriate diagnostic and therapeutic strategies for sepsis and current management rely on the limited treatment strategies. Recently, nanomedicines targeting and controlling the release of bio-active agents have shown excellent potency in sepsis management, with improved therapeutic efficacy and reduced adverse effects. In this review, we have summarized the advantages of nanomaterials. Also, the preparation and efficacy of the main categories of anti-sepsis nanomedicines applied in sepsis management are described in detail, including antibiotic-coated nanomaterials, antimicrobial peptides-coated nanomaterials, biomimetic nanomaterials, nanomaterials targeting macrophages and natural products loaded nanomaterials. These advances in nanomedicines establish the huge potential for nanomaterials-based sepsis management, especially in the improved pharmaceutical and pharmacological properties, enhanced therapeutic efficacy, controllable drug-targeting and reduced side effects. To further facilitate clinical translation of anti-sepsis nanomedicines, we propose that the issues involving safety, regulatory laws and cost-effectiveness should receive much more attention in the future.

Background. Gout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown. Objectives. To explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification. Methods. The ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-κB, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining. Results. 48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, ()-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1β, TNF-α, and p38. The data from in vitro experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-κB, and NLRP3 signaling pathways. Conclusion. Our finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-κB, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.