Inflammatory bowel disease (IBD), a widespread intestinal disease threatening human health, is commonly accompanied by secondary liver injury (SLI). Pyroptosis and oxidative stress act as an important role underlying the pathophysiology of SLI, during which a large number of proinflammatory cytokines and oxidative intermediates can be produced, thereby causing the liver severely damaged. Suppression of pyroptosis and oxidative damage can be considered one of the critical strategies for SLI therapy. Garlic, a natural food with eatable and medicinal functions, is widely used in people’s daily life. There is no study about the alleviation of garlic against IBD accompanied with SLI. This study is aimed at investigating the efficacy of the polysaccharides from garlic (PSG) in treating IBD and SLI, as well as its pharmacological mechanism. The results showed that PSG significantly alleviated dextran sulfate sodium‐induced IBD determined by evaluating the bodyweight loss, disease activity index, colon length, and colonic pathological examination of mice. PSG significantly reduced the colonic inflammation by reversing the levels of myeloperoxidase, diamine oxidase activity, iNOS, and COX2 and strengthened the intestinal barrier by increasing the expressions of ZO1, occludin, and MUC2 of IBD mice. Furthermore, PSG strongly alleviated SLI determined by assessing the liver morphological change, liver index, levels of ALT and AST, and liver pathological change of mice. Mechanically, PSG reduced the high levels of LPS, IL‐1β, IL18, NLRP3, gasdermin D, caspase 1, ASC, TLR4, MyD88, NF‐κB, phospho‐NF‐κB, while it increased IL‐10 in the livers of mice, indicating that PSG alleviated SLI by suppressing inflammation and pyroptosis. Additionally, PSG significantly inhibited the oxidative damage in the liver tissues of SLI mice by reducing the levels of ROS, MDA, Keap‐1, 8‐OHDG, and phospho‐H2AX and increasing the levels of GPX4, SOD2, HO1, NQO1, and Nrf2. These findings suggested that the garlic polysaccharides could be used to treat IBD accompanied with SLI in humans.

Colorectal cancer (CRC) is one of the most common malignancies and most frequent cause of cancer death worldwide. The activation of both NF‐κB and STAT3 signaling and the crosstalk between them play an important role in colorectal tumor. Helicteres angustifolia L. is a type of commonly used Chinese medicinal herb and possesses a wide variety of biological activities. In the present study, we investigate the effects of three triterpenes from H. angustifolia (HT) such as helicteric acid (HA), oleanic acid (OA), and betulinic acid (BA), on inhibiting CRC progression. Our results showed that HT extracts could decrease proliferation and induce apoptosis in HT‐29 colorectal cancer cells. Moreover, HT extracts could suppress LPS‐triggered phosphorylation of IKK, IκB, and NF‐κB, attenuate IL‐6‐induced phosphorylation of JAK2 and STAT3, and suppress the expression of c‐Myc, cyclin‐D1, and BCL‐xL, the downstream gene targets of NF‐κB and STAT3. Therefore, HT extracts showed potent therapeutic and antitumor effects on CRC via inhibiting NF‐κB and STAT3 signaling.

Background: Ardisia gigantifolia Stapf. (AGS), a Chinese folk medicine widely grows in the south of China and several studies reported that AGS could inhibit the proliferation of breast cancer, liver cancer, and bladder cancer cell lines. However, little is known about its anti-colorectal cancer (CRC) efficiency. Methods: In the present study, a combination of MTT assay, network pharmacological analysis, bioinformatics, molecular docking, and molecular dynamics simulation study was used to investigate the active ingredients, and targets of AGS against CRC, as well as the potential mechanism. Results: MTT assay showed that three kinds of fractions from AGS, including the n-butanol extract (NBAGS), ethyl acetate fraction (EAAGS), and petroleum ether fraction (PEAGS) significantly inhibited the proliferation of CRC cells, with the IC₅₀ values of 197.24, 264.85, 15.45 µg/mL on HCT116 cells, and 523.6, 323.59, 150.31 µg/mL on SW620 cells, respectively. Eleven active ingredients, including, 11-O-galloylbergenin, 11-O-protocatechuoylbergenin, 11-O-syringylbergenin, ardisiacrispin B, bergenin, epicatechin-3-gallate, gallic acid, quercetin, stigmasterol, stigmasterol-3-o-β-D-glucopyranoside were identified. A total of 173 targets related to the bioactive components and 21,572 targets related to CRC were picked out through database searching. Based on the crossover targets of AGS and CRC, a protein-protein interaction network was built up by the String database, from which it was concluded that the core targets would be SRC, MAPK1, ESR1, HSP90AA1, MAPK8. Besides, GO analysis showed that the numbers of biological process, cellular component, and molecular function of AGS against CRC were 1079, 44, and 132, respectively, and KEGG pathway enrichment indicated that 96 signaling pathways in all would probably be involved in AGS against CRC, among which MAPK signaling pathway, lipid, and atherosclerosis, proteoglycans in cancer, prostate cancer, adherens junction would probably be the major pathways. The docking study verified that AGS had multiple ingredients and multiple targets against CRC. Molecular dynamics (MD) simulation analysis showed that the binding would be stable via forming hydrogen bonds. Conclusion: Our study showed that AGS had good anti-CRC potency with the characteristics of multi-ingredients, -targets, and -signaling pathways.

Polygoni Vivipari Rhizoma (PVR), the dried root of Polygonum viviparum, has been used as herbal medicine in China for a long time. In the present study, a new method based on multi-step matrix solid-phase dispersion (MSPD), ultrafiltration and high performance liquid chromatography (HPLC) for screening alpha-glucosidase inhibitors (AGIs) from PVR was proposed. First, three different PVR extractions were prepared by multi-step MSPD with 15% methanol, 60% methanol and 100% methanol. Second, the alpha-glucosidase inhibition tests for the three extracts were carried out, and the 60% methanol extraction showed the best activity. Then, the AGIs screening experiment was performed with ultrafiltration and HPLC analysis using the 60% methanol extraction. Seven binding components (quercetin−3−O−vicianoside, quercetin 3−O−neohesperidoside, rutin, hyperoside, quercetin 3−O−glucuronide, luteolin−7−O−neohesperidoside, kaempferol 3−glucuronide) were found. These seven components were further validated as the AGIs by molecular docking analysis. The developed method was a rapid and efficient tool for screening AGIs from PVR, which provided scientific data for the bioactive components study of PVR.

Ficus pandurata Hance (FPH) is a Chinese herbal medicine widely used for health care. This study was designed to investigate the alleviation efficacy of the low-polarity ingredients of FPH (FPHLP), prepared by supercritical CO₂ fluid extraction technology, against CCl₄-induced acute liver injury (ALI) in mice and uncover its underlying mechanism. The results showed that FPHLP had a good antioxidative effect determined by the DPPH free radical scavenging activity test and T-AOC assay. The in vivo study showed that FPHLP dose-dependently protected against liver damage via detection of ALT, AST, and LDH levels and changes in liver histopathology. The antioxidative stress properties of FPHLP suppressed ALI by increasing levels of GSH, Nrf2, HO-1, and Trx-1 and reducing levels of ROS and MDA and the expression of Keap1. FPHLP significantly reduced the level of Fe²⁺ and expression of TfR1, xCT/SLC7A11, and Bcl2, while increasing the expression of GPX4, FTH1, cleaved PARP, Bax, and cleaved caspase 3. The results demonstrated that FPHLP protected mouse liver from injury induced by CCl₄ via suppression of apoptosis and ferroptosis. This study suggests that FPHLP can be used for liver damage protection in humans, which strongly supports its traditional use as a herbal medicine.

The Janus kinases (JAKs) consist of four similar tyrosine kinases and function as key hubs in the signaling pathways that are implicated in both innate and adaptive immunity. Among the four members, JAK3 is probably the more attractive target for treatment of inflammatory diseases because its inhibition demonstrates the greatest immunosuppression and most profound effect in the treatment of such disorders. Although many JAK3 inhibitors are already available, certain shortcomings have been identified, mostly acquired drug resistance or unwanted side effects. To discover and identify new promising lead candidates, in this study, the structure of JAK3 (3LXK) was obtained from the Protein Data Bank and used for simulation modeling and protein-ligand interaction analysis. The ~36,000 Chinese herbal compounds obtained from TCM Database@Taiwan were virtually screened by AutoDock Vina docking program and filtered with Lipinski’s Rules and ADME/T virtual predictions. Because of high occurrence of fake hits during docking, we selected 12 phytochemicals which have demonstrated modulating JAKs expressions among the top 50 chemicals from docking results. To validate whether these compounds are able to directly mediate JAK3 kinase, we have investigated the inhibitory activity using enzymatic activity assays, western blot, and HEK 293 cell STAT5 transactivity assays. The molecular analysis included docking and molecular dynamics (MD) simulations in order to investigate structural conformations and to explore the key amino acids in the interaction between JAK3 kinase and its putative ligands. The results demonstrated that Cryptotanshinone, Icaritin, and Indirubin exhibited substantial inhibitory activity against JAK3 kinase in vitro. The results also provide binding models of the protein-ligand interaction, detailing the interacting amino acid residues at the active ATP-binding domains of JAK3 kinase. In conclusion, our work discovered 3 potential natural inhibitors of JAK3 kinase and could provide new possibilities and stimulate new insights for the treatment of JAK3-targeted diseases.