The Huashi Baidu Formula (HSBDF), a key Chinese medical drug, has a remarkable clinical efficacy in treating acute lung injury (ALI), and it has been officially approved by the National Medical Products Administration of China for drug clinical trials. Nevertheless, the regulated mechanisms of HSBDF and its active compounds in plasma against ALI were rarely studied. Based on these considerations, the key anti-inflammatory compounds of HSBDF were screened by molecular docking and binding free energy. The key compounds were further identified in plasma by LC/MS. Network pharmacology was employed to identify the potential regulatory mechanism of the key compounds in plasma. Next, the network pharmacological prediction was validated by a series of experimental assays, including CCK-8, EdU staining, test of TNF-α, IL-6, MDA, and T-SOD, and flow cytometry, to identify active compounds. Molecular dynamic simulation and binding interaction patterns were used to evaluate the stability and affinity between active compounds and target. Finally, the active compounds were subjected to predict pharmacokinetic properties. Molecular docking revealed that HSBDF had potential effects of inhibiting inflammation by acting on IL-6R and TNF-α. Piceatannol, emodin, aloe-emodin, rhein, physcion, luteolin, and quercetin were key compounds that may ameliorate ALI, and among which, there were five compounds (emodin, aloe-emodin, rhein, luteolin, and quercetin) in plasma. Network pharmacology results suggested that five key compounds in plasma likely inhibited ALI by regulating inflammation and oxidative damage. Test performed in vitro suggested that HSBDF (0.03125 mg/ml), quercetin (1.5625 μM), emodin (3.125 μM), and rhein (1.5625 μM) have anti-inflammatory function against oxidative damage and decrease apoptosis in an inflammatory environment by LPS-stimulation. In addition, active compounds (quercetin, emodin, and rhein) had good development prospects, fine affinity, and stable conformations with the target protein. In summary, this study suggested that HSBDF and its key active components in plasma (quercetin, emodin, and rhein) can decrease levels of pro-inflammatory factors (IL-6 and TNF-α), decrease expression of MDA, increase expression of T-SOD, and decrease cell apoptosis in an inflammatory environment. These data suggest that HSBDF has significant effect on anti-inflammation and anti-oxidative stress and also can decrease cell apoptosis in treating ALI. These findings provided an important strategy for developing new agents and facilitated clinical use of HSBDF against ALI.

Deciphering the Active Compounds and Mechanisms of HSBDF for Treating ALI via Integrating Chemical Bioinformatics Analysis

Sea buckthorn (Hippophae rhamnoides L.), an ancient miraculous plant, is of great interest because of its tenacity, richness in nutritional active substances, and biological activity. Sea buckthorn is a deciduous shrub or tree of the genus Hippophae in the family Elaeagnaceae. It is a pioneer tree species for soil improvement, wind and sand control, and soil and water conservation. Sea buckthorn contains many nutritional active components, such as vitamins, carotenoids, polyphenols, fatty acids, and phytosterols. Moreover, sea buckthorn has many health benefits, such as antioxidant, anticancer, anti-hyperlipidemic, anti-obesity, anti-inflammatory, antimicrobial, antiviral, dermatological, neuroprotective, and hepatoprotective activities. Sea buckthorn not only has great medicinal and therapeutic potential, but also is a promising economic plant. The potential of sea buckthorn in the human food industry has attracted the research interest of researchers and producers. The present review mainly summarizes the phytochemistry, nutrients, health benefits, and food applications of sea buckthorn. Overall, sea buckthorn is a dietary source of bioactive ingredients with the potential to be developed into functional foods or dietary supplements for the prevention and treatment of certain chronic diseases, which deserves further research.

/pdf/phytochemistry-health-benefits-and-food-applications-of-sea-5p5lmgma.pdf

Phytochemistry, health benefits, and food applications of sea buckthorn (Hippophae rhamnoides L.): A comprehensive review

Cancer is a global public health problem that is related to different environmental and lifestyle factors. Although the combination of screening, prevention, and treatment of cancer has resulted in increased patient survival, conventional treatments sometimes have therapeutic limitations such as resistance to drugs or severe side effects. Oriental culture includes herbal medicine as a complementary therapy in combination with chemotherapy or radiotherapy. This study aimed to identify the bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach. The herb contains gallic acid, caffeic acid, coumaric acid, quercetin, quercitrin, isorhamnetin, kaempferol, bersaldegenin, bryophyllin a, bryophyllin c, bryophynol, bryophyllol and bryophollone, stigmasterol, campesterol, and other elements. Its phytochemicals participate in the regulation of proliferation, apoptosis, cell migration, angiogenesis, metastasis, oxidative stress, and autophagy. They have the potential to act as epigenetic drugs by reverting the acquired epigenetic changes associated with tumor resistance to therapy—such as the promoter methylation of suppressor genes, inhibition of DNMT1 and DNMT3b activity, and HDAC regulation—through methylation, thereby regulating the expression of genes involved in the PI3K/Akt/mTOR, Nrf2/Keap1, MEK/ERK, and Wnt/β-catenin pathways. All of the data support the use of K. pinnata as an adjuvant in cancer treatment.

https://www.mdpi.com/1420-3049/27/19/6425/pdf?version=1664531348

Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator

Effect and mechanism of Kangfuxin liquid on oral ulcer in patients with chemotherapy treated hematologic malignancies: Network pharmacology study and clinical observations

Isoquercitrin Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Gastric Cancer Cells

Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K‐AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1‐ligand 1 (PD‐L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD‐L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD‐L1, with K d values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD‐L1, calculated by molecular mechanics Poisson‐Boltzmann surface area, of −26.55, −14.18, −19.41, and −11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN‐45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.14851

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.

A tumor-related hypoxic microenvironment can promote the proliferation of gastric cancer cells, and hypoxic-induced autophagy is the main mechanism of protection against hypoxia in gastric cancer cells. Isorhamnetin (ISO) is a chemical substance derived from plants, mainly from the sea buckthorn. Previous studies have shown that ISO has antitumor effects, but the effects of ISO against gastric cancer in a hypoxic environment are still unknown. In this study, we investigated the effects of ISO against gastric cancer in a hypoxic environment and the mechanisms underlying ISO-induced gastric cancer cell death. The results show that ISO targeted PI3K and blocked the PI3K-AKT-mTOR signaling pathway, significantly inhibiting gastric cancer cell autophagy in a hypoxic environment, inhibiting cell proliferation, decreasing mitochondrial membrane potential, and promoting mitochondria-mediated apoptosis. ISO, a functional food component, is a promising candidate for the treatment of gastric cancer.

Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment.

What is known and objective An increasing number of targeted drugs have been used to treat advanced or metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, the optimal treatment efficacy of these drugs is still controversial. The aims of this study are to systematically summarize the efficacy and safety of current targeted drugs for advanced or metastatic GC and GEJC. Methods PubMed, EmBase, Cochrane Library, Web of Science and ClinicalTrials were searched for double-blind randomized controlled trials (RCTs) on GC and GEJC up to December 2019. Additionally, we updated the literature search from Jan, 1, 2020 to September 30, 2021. Narrative and quantitative analysis were performed to analyse the efficacy and safety. STATA 15.1 was used to identify publication bias, and the SUCRA (surface under the cumulative ranking) curve was conducted to rank the treatments for each outcome. Results A total of 27 RCTs with 9295 GC and GEJC patients treated by 19 drugs were included. SUCRA showed that regorafenib was the most likely to improve patients' progression-free survival (96.4%), followed by apatinib (90.7%), nivolumab (82.4%), everolimus (76.5%) and pertuzumab (68.5%). Meanwhile, apatinib (92.4%) was most likely to improve overall survival, followed by nivolumab (87.9%), regorafenib (72.5%), olaparib (67.7%) and lapatinib (63.2%). Additionally, neutropenia, diarrhoea and fatigue were the most common adverse events caused by these drugs, followed by pain, nausea, decreased appetite, anaemia and vomiting. What is new and conclusion Regorafenib and nivolumab have higher efficacy and tolerability and are the most advantageous for advanced GC and GEJC. Moreover, apatinib has higher efficacy but lower tolerability. Everolimus and pertuzumab combined with chemotherapy have best secondary higher efficacy for progression-free survival and good tolerability. Lapatinib and olaparib combined with chemotherapy have moderate efficacy for overall survival and good tolerability.

Efficacy and safety of targeted drugs in advanced or metastatic gastric and gastroesophageal junction cancer: A network meta-analysis.

Gastric cancer (GC) is a globally important disease. Targeted therapies licensed to treat gastric cancer include trastuzumab, which targets HER2, and nivolumab or pembrolizumab, which block PD-1/PD-L1. The main challenge of tumor molecule-targeted drugs is resistance. Based on the multicomponent and multitarget characteristics of Traditional Chinese Medicine (TCM) and our previous research on Guiqi Baizhu Prescription (GQBZP) in targeting HER2/PD-L1, we used different cell models to verify the effect of quercetin targeting of HER2 and formononetin targeting of PD-L1. The results show that quercetin can inhibit MKN-45 cell proliferation by targeting HER2 to inhibit the PI3K-AKT pathway, and formononetin can regulate T-cell function by inhibiting the PD-1/PD-L1 pathway. We also used gastric cancer MKN-45 cells in a T lymphocyte co-culture model to show that quercetin and formononetin co-treatment can regulate T cell function and inhibit MKN-45 cell proliferation. More importantly, quercetin with formononetin treatment had a greater effect than treatment with either quercetin or formononetin alone. We believe that quercetin and formononetin may be useful to target HER2 and inhibit PD-1/PD-L1 in gastric cancer.

Xiaojie Jin

Papers

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.

Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment.

Efficacy and safety of targeted drugs in advanced or metastatic gastric and gastroesophageal junction cancer: A network meta-analysis.

A combination therapy of Ingredients from TCM for the prevention and treatment of gastric cancer by targeting HER2/ PD-L1