Shuang-huang-lian injection (SHLI) is a famous Chinese patent medicine, which has been wildly used in clinic for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. The existing randomized controlled trial (RCT) studies suggested that SHLI could afford a certain anti-febrile action. However, seldom does research concern the pharmacological mechanisms of SHLI. In the current study, we explored plasma metabolomic profiling technique and selected potential metabolic markers to reveal the antipyretic mechanism of SHLI on yeast-induced pyrexia rat model using UPLC-Q-TOF/MS coupled with multivariate statistical analysis and pattern recognition techniques. We discovered a significant perturbance of metabolic profile in the plasma of fever rats and obvious reversion in SHLI-administered rats. Eight potential biomarkers, i.e. 1) 3-hydeoxybutyric acid, 2) leucine, 3) 16∶0 LPC, 4) allocholic acid, 5) vitamin B₂, 6) Cys-Lys-His, 7) 18∶2 LPC, and 8) 3-hydroxychola-7, 22-dien-24-oic acid, were screened out by OPLS-DA approach. Five potential perturbed metabolic pathways, i.e. 1) valine, leucine, and isoleucine biosynthesis, 2) glycerophospholipid metabolism, 3) ketone bodies synthesis and degradation, 4) bile acid biosynthesis, and 5) riboflavin metabolism, were revealed to relate to the antipyretic mechanisms of SHLI. Overall, we investigated antipyretic mechanisms of SHLI at metabolomic level for the first time, and the obtained results highlights the necessity of adopting metabolomics as a reliable tool for understanding the holism and synergism of Chinese patent drug.

Background and aims: This study aims to investigate whether the Dietary Inflammatory Index (DII) is associated with non-alcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF) among non-institutionalized adults in the United States.Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016, a total of 10,052 adults aged ≥18 years were included in the analysis. We used multivariable analysis, controlling for demographic variables, to evaluate the association between DII and NAFLD and AHF, a restricted cubic spline (RCS) was used to model the non-linear relationship between DII and NAFLD.Results: For 10,052 participants, DII ranges from -4.63 to 5.47. Compared with quartile 1, higher DII group were associated with higher levels of female, separated/divorced, lower education level, heavy alcohol use, current smoke status, BMI, poverty income ratio, and waist circumference. DII also showed a significantly positive correlation with ALT, AST. In the fully adjusted multivariable model, DII was positively associated with the presence of NAFLD (OR 1.09, 1.06–1.13 CI, p trend <0.0001), and AHF (OR 1.15, 1.07–1.23 CI, p trend <0.001). The association remained statistically significant after stratified by gender in terms of NAFLD, but in case of AHF only in males (Q4 vs. Q1: OR 2.68, 1.63–4.41 CI, p trend <0.0001) was statistically significant. In the RCS models, the relation of DII and NAFLD started increase rapidly until around 1.80 and then started relatively flat afterward.Conclusion: Higher pro-inflammatory level was associated with higher risk of NAFLD in males and females, and with higher risk of AHF in males but not in females. Therefore, strategies to promote an Zhang anti-inflammatory diet should be considered to prevent and ameliorate NAFLD and AHF in adults.

Triptolide, a controversial natural compound due to its significant pharmacological activities and multiorgan toxicity, has gained much attention since it was isolated from the traditional Chinese herb Tripterygium wilfordii Hook F. However, in addition to its severe toxicity, triptolide also presents powerful therapeutic potency in the same organs, such as the liver, kidney, and heart, which corresponds to the Chinese medicine theory of You Gu Wu Yun (anti-fire with fire) and deeply interested us. To determine the possible mechanisms involved in the dual role of triptolide, we reviewed related articles about the application of triptolide in both physiological and pathological conditions. Inflammation and oxidative stress are the two main ways triptolide exerts different roles, and the cross-talk between NF-κB and Nrf2 may be one of the mechanisms responsible for the dual role of triptolide and may represent the scientific connotation of You Gu Wu Yun. For the first time, we present a review of the dual role of triptolide in the same organ and propose the possible scientific connotation of the Chinese medicine theory of You Gu Wu Yun, hoping to promote the safe and efficient use of triptolide and other controversial medicines.

Guizhi-Shaoyao-Zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.

Semen Cuscutae is a well‐known Chinese medicine which has been used to nourish kidney in China for thousands of years. The crude product of semen Cuscutae (CP) and its salt‐processed product (SPP) are separately used in clinic for their different effects. The study was designed to investigate the influence of processing from semen Cuscutae on chemical components and biological effects. The principal component analysis and quantitative analysis were used to study the differences of the chemical components. The effects of nourishing kidney were detected to compare the differences between the CP and SPP. The PCA results showed that the obvious separation was achieved in the CP and SPP samples. The results of quantitative analysis showed that quercetin and total flavonoids had significantly increased after salt processing while hyperoside had decreased. The comparison of CP and SPP on biological activities showed that both of them could ameliorate the kidney‐yang deficiency syndrome by restoring the level of sex hormone, improving the immune function and antioxidant effect. However, SPP was better in increasing the level of T and the viscera weight of testicle and epididymis, improving the antioxidant effect. The results suggested that salt processing changed its chemical profile, which in turn enhanced its biological activities.

Chronic inflammation within the tumor microenvironment (TME) is a critical driver of immune evasion, resistance to therapy, and progression of cancer, whil