Lianhua Qingwen exerts anti-liver cancer effects and synergistic efficacy with sorafenib through PI3K/AKT pathway: Integrating network pharmacology, molecular docking, and experimental validation.

Liver cancer is one of the most lethal malignancies and sorafenib resistance is the main treatment obstacle for patients with advanced liver cancer. Developing drugs that sensitize liver cancer patients to sorafenib is of great importance. Lianhua Qingwen (LHQW), a sort of Traditional Chinese Medicine (TCM) approved by the Chinese Food and Drug Administration (CFDA), is reported to exert synergistic effects with oseltamivir against Influenza virus. However, whether LHQW could exhibit anti-liver cancer effects and enhance the efficacy of sorafenib against liver cancer have not been reported. In the present study, the potential anti-liver cancer effects of LHQW and its synergistic effects with sorafenib were investigated via applying network pharmacology, molecular docking, and in vitro experiments. An "ingredient-compound- target-liver cancer" network was constructed which included 12 ingredients, 164 compounds, and 402 targets. AKT1 was identified as the most hub gene and the PI3K/AKT pathway was revealed as the most enriched pathway. Subsequently, the molecular docking results showed that kaempferol, luteolin, and quercetin were screened as the top 3 compounds which showed the tightest binding to AKT1. Further, the in vitro experiments verified that LHQW significantly inhibited liver cancer cell proliferation and induced apoptosis. Western blot assays confirmed that LHQW could attenuate the PI3K/AKT pathway. Interestingly, LHQW showed a synergistic effect with sorafenib against liver cancer via reducing cell viability, inducing apoptosis, and down- regulating PI3K/AKT pathway. This study broadens the potential application of LHQW and provides insights for liver cancer treatment.

Synergist for antitumor therapy: Astragalus polysaccharides acting on immune microenvironment.

Various new treatments are emerging constantly in anti-tumor therapies, including chemotherapy, immunotherapy, and targeted therapy. However, the efficacy is still not satisfactory. Astragalus polysaccharide is an important bioactive component derived from the dry root of Radix astragali. Studies found that astragalus polysaccharides have gained great significance in increasing the sensitivity of anti-tumor treatment, reducing the side effects of anti-tumor treatment, reversing the drug resistance of anti-tumor drugs, etc. In this review, we focused on the role of astragalus polysaccharides in tumor immune microenvironment. We reviewed the immunomodulatory effect of astragalus polysaccharides on macrophages, dendritic cells, natural killer cells, T lymphocytes, and B lymphocytes. We found that astragalus polysaccharides can promote the activities of macrophages, dendritic cells, natural killer cells, T lymphocytes, and B lymphocytes and induce the expression of a variety of cytokines and chemokines. Furthermore, we summarized the clinical applications of astragalus polysaccharides in patients with digestive tract tumors. We summarized the effective mechanism of astragalus polysaccharides on digestive tract tumors, including apoptosis induction, proliferation inhibition, immunoactivity regulation, enhancement of the anticancer effect and chemosensitivity. Therefore, in view of the multiple functions of astragalus polysaccharides in tumor immune microenvironment and its clinical efficacy, the combination of astragalus polysaccharides with antitumor therapy such as immunotherapy may provide new sparks to the bottleneck of current treatment methods.

Synthesis and biological evaluation of matrine derivatives containing benzo-α-pyrone structure as potent anti-lung cancer agents.

Matrine, an active component of root extracts from Sophora flavescens Ait, is the main chemical ingredient of Fufang Kushen injection which was approved by Chinese FDA (CFDA) in 1995 as an anticancer drug to treat non-small cell lung cancer and liver cancer in combination with other anticancer drugs. Owning to its druggable potential, matrine is considered as an ideal lead compound for modification. We delineate herein the synthesis and anticancer effects of 17 matrine derivatives bearing benzo-α-pyrone structures. The results of cell viability assays indicated that most of the target compounds showed improved anticancer effects. Further studies showed that compound 5i could potently inhibit lung cancer cell proliferation in vitro and in vivo with no obvious side effects. Moreover, compound 5i could induce G1 cell cycle arrest and autophagy in lung cancer cells through up-regulating P27, down-regulating CDK4 and cyclinD1 and attenuating PI3K/Akt/mTOR pathway. Suppression of autophagy attenuated 5i induced proliferation inhibition. Collectively, our results infer that matrine derivative 5i bears therapeutic potentials for lung cancer.

Study of the interaction between sodium salts of (2E)-3-(4'-halophenyl)prop-2-enoyl sulfachloropyrazine and bovine serum albumin by fluorescence spectroscopy.

Three sodium salts of (2E)-3-(4'-halophenyl)prop-2-enoyl sulfachloropyrazine (CCSCP) were synthesized and their structures were determined by (1)H and (13)C NMR, LC-MS and IR. The binding properties between CCSCPs and bovine serum albumin (BSA) were studied using fluorescence spectroscopy in combination with UV-vis absorbance spectroscopy. The results indicate that the fluorescence quenching mechanisms between BSA and CCSCPs were static quenching at low concentrations of CCSCPs or combined quenching (static and dynamic) at higher CCSCP concentrations of 298, 303 and 308 K. The binding constants, binding sites and corresponding thermodynamic parameters (ΔH, ΔS, ΔG) were calculated at different temperatures. All ΔG values were negative, which revealed that the binding processes were spontaneous. Although all CCSCPs had negative ΔH and positive ΔS, the contributions of ΔH and ΔS to ΔG values were different. When the 4'-substituent was fluorine or chlorine, van der Waals interactions and hydrogen bonds were the main interaction forces. However, when the halogen was bromine, ionic interaction and proton transfer controlled the overall energetics. The binding distances between CCSCPs and BSA were determined using the Förster non-radiation energy transfer theory and the effects of CCSCPs on the conformation of BSA were analyzed by synchronous fluorescence spectroscopy.