Salvia miltiorrhiza Bunge (Danshen) based nano-delivery systems for anticancer therapeutics.

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.

Experimental Research on the Antitumor Effect of Human Gastric Cancer Cells Transplanted in Nude Mice Based on Deep Learning Combined with Spleen-Invigorating Chinese Medicine.

Gastric cancer is still the fifth most common malignant tumor in the world and has the fourth highest mortality rate in the world. Gastric cancer is difficult to treat because of its unobvious onset, low resection rate, and rapid deterioration. Therefore, humans have been working hard to combat gastric cancer. At present, the most commonly used treatment method is radiotherapy. However, this method will damage the normal tissues of the irradiated area while treating malignant tumor cells. It not only has side effects of damage to the patient's skin and mucous membranes but also needs high-rate radiotherapy and has high cost for chemotherapy. In order to solve these problems, it is necessary to find new treatment methods. This article proposes the use of Chinese medicine to invigorate the spleen to inhibit human gastric cancer cells. This article combines modern machine learning technology with traditional Chinese medicine and combines traditional Chinese medicine physiotherapy with Western medicine nude mouse transplantation experiments. The treatment of tumors in Chinese medicine is based on the theory of Chinese medicine and has different characteristics. Western medicine has the advantage of permanently injuring patients. The process of the experiment is to transplant human-derived gastric cancer cells into nude mice. After grouping treatments and obtaining comparative data, deep learning techniques are used to analyze the properties of Chinese medicines for strengthening the spleen and to compare the properties of Chinese medicines for strengthening the spleen. The experimental results showed that the tumor inhibition rate of mice using fluorouracil was 18%, the tumor inhibition rate of mice using low-dose Chinese medicine was 16%, and the tumor inhibition rate of mice using high-dose Chinese medicine reached 52%. 80 days after the experiment, the survival rate of mice using high-dose Chinese medicine is 100% higher than that of mice without treatment.

Design of Turmeric Rhizome Extract Nano-Formula for Delivery to Cancer Cells.

Novel turmeric rhizome extract nanoparticles (TE-NPs) were developed from fractions of dried turmeric (Curcuma longa Linn.) rhizome. Phytochemical studies, by using HPLC and TLC, of the fractions obtained from ethanol extraction and solvent-solvent extraction showed that turmeric rhizome ethanol extract (EV) and chloroform fraction (CF) were composed mainly of three curcuminoids and turmeric oil. Hexane fraction (HE) was composed mainly of turmeric oil while ethyl acetate fraction (EA) was composed mainly of three curcuminoids. The optimal TE-NPs formulation with particle size of 159.6 ± 1.7 nm and curcumin content of 357.48 ± 8.39 µM was successfully developed from 47-run D-optimal mixture-process variables experimental design. Three regression models of z-average, d50, and d90 could be developed with a reasonable accuracy of prediction (predicted r2 values were in the range of 0.9120-0.9992). An in vitro cytotoxicity study using MTT assay demonstrated that the optimal TE-NPs remarkably exhibited the higher cytotoxic effect on human hepatoma cells, HepG2, when compared with free curcumin. This study is the first to report nanoparticles prepared from turmeric rhizome extract and their cytotoxic activity to hepatic cancer cells compared with pure curcumin. These nanoparticles might serve as a potential delivery system for cancer therapy.

Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer.

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.

Cytotoxic terpenoids from Tripterygium hypoglaucum against human pancreatic cancer cells SW1990 by increasing the expression of Bax protein.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium hypoglaucum (Kunmingshanhaitang in Chinese) is a plant of the genus Tripterygium which have been used as anti-tumor folk medicines in Yi and Bai ethnic groups in Yunnan province, China for hundreds of years. Terpenoids from T. hypoglaucum presented therapeutic effects on multiple tumors. But there were few studies about pancreatic cancer treatment of these terpenoids. Pancreatic cancer is an aggressive malignancy and lacked of specific drugs. Currently, anti-tumor drugs have poor therapeutic effect and prognosis for pancreatic cancer. AIM OF THE STUDY: This study aimed to elucidate the terpenoids from T. hypoglaucum and illuminate their anti-pancreatic cancer bioactivities. MATERIAL AND METHODS: Terpenoids were obtained through sequential chromatographic methods including silica gel, MCI gel, Sephadex LH-20, and preparative HPLC. Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopic analysis. The absolute configurations of some new diterpenoids were assigned through comparison of experimental and calculated circular dichroism spectra. The cytotoxicity of isolates was measured using the MTT method on human pancreatic cancer cells SW1990. The effects on expressions of AKT, Erk1/2, p-AKT, p-Erk1/2, and Bax proteins in human pancreatic cancer cells SW1990 of these compounds were determined by western blotting assays. RESULTS: Eleven new (compounds 1∼11) and fourteen known terpenoids (compounds 12∼25) were isolated from the underground parts of T. hypoglaucum. These compounds were belonged to abietane diterpenoids, isoprimara diterpenoids, ent-kaurane diterpenoids, oleanane triterpenoids, and friedelane triterpenoids. Compounds 5, 7, 8, 9, 16, 18, 22, 24, and 25 possessed significant cytotoxicity against SW1990 cells with IC50 values of 19.28 ± 4.39, 9.91 ± 2.23, 27.32 ± 5.89, 56.43 ± 6.92, 0.16 ± 0.05, 0.58 ± 0.15, 0.81 ± 0.04, 0.48 ± 0.11, and 10.01 ± 1.39 µM respectively. After compounds 16, 22, and 24 been treated with the pancreatic cancer cells in medium and high doses, the protein expressions of AKT, p-AKT, Erk, and p-Erk were not remarkably reduced and the expressions of Bax protein were significantly increased. CONCLUSION: This study indicated that terpenoids from T. hypoglaucum could inhibit human pancreatic cancer cells SW1990. Especially, compounds 16, 22, and 24 possessed significant cytotoxicity against SW1990 cells with low IC50 values and could increase the expressions of Bax protein. These compounds shared a wide variety of structural characteristics which provided us more candidate molecules for the development of anti-pancreatic cancer drugs and further prompted us to investigate their anti-pancreatic mechanisms.

Cytotoxic effect of hydroalcoholic extract of Cota tinctoria (L) J. Gay on AGS and Hep-G2 cancer cell lines / Efecto citotóxico del extracto hidroalcohólico de Cota tinctoria (L) J. Gay sobre líneas celulares de cáncer AGS y Hep-G2

Cota tinctoria is a medicinal plant which has been used for management of cancer in folk medicine of various regions. The aim of present study is to investigate cytotoxic activity of different concentrations of hydroalcoholic extract of C. tinctoria flowers on gastric (AGS) and liver (Hep-G2) cancer cell lines as well as Human Natural GUM fibroblast (HUGU) cells. Cell mortality rates were examined after 24, 48 and 72 h incubations using the MTT assay. IC50of extract on AGS cells after 24, 48 and 72h was 1.46, 1.29 and 1.14 µg/mL respectively. The extract demonstrated IC50 of 5.15, 3.92 and 2.89 µg/mL on Hep-G2 cells after 24, 48 and 72 h respectively. No cytotoxic effect was detected on HUGU (Human Natural GUM fibroblast) cells. C. tinctoria seems to have a promising potential to be considered as a source for anticancer drug discovery. However, more experimental and clinical studies are required.

Cota tinctoria es una planta medicinal que se ha utilizado para el tratamiento del cáncer en la medicina popular de varias regiones. El objetivo del presente estudio es investigar la actividad citotóxica de diferentes concentraciones de extracto hidroalcohólico de flores de C. tinctoria en líneas celulares de cáncer gástrico (AGS) e hígado (Hep-G2), así como en células de fibroblasto GUM humano natural (HUGU). Se examinaron las tasas de mortalidad celular después de incubaciones de 24, 48 y 72 h utilizando el ensayo MTT. La CI50 del extracto en células AGS después de 24, 48 y 72 h fue de 1,46; 1,29 y 1,14 µg respectivamente. El extracto demostró una CI50 de 5,15, 3,92 y 2,89 µg/mL en células Hep-G2 después de 24, 48 y 72 h, respectivamente. No se detectó ningún efecto citotóxico en las células HUGU (fibroblasto GUM humano natural). C. tinctoria parece tener un potencial prometedor para ser considerada como una fuente de descubrimiento de fármacos contra el cáncer. Sin embargo, se requieren más estudios experimentales y clínicos.

Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway.

Oleandrigenin-3-O-ß-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-ß-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and caspase-9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML).

Marantodes pumilum: Systematic computational approach to identify their therapeutic potential and effectiveness.

ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (MP) herbs, locally known as Kacip Fatimah, are widely used traditionally to improve women's health. The herb is frequently used for gynecological issues such as menstrual problems, facilitating and quickening delivery, post-partum medication, treats flatulence and dysentery, and. MP extracts are thought to aid in the firming and toning of abdominal muscles, tighten breasts and vaginal muscles, and anti-dysmenorrhea. It also was used for the treatment of gonorrhea and hemorrhoids. As MP product has been produced commercially recently, more in-depth studies should be conducted. The presence of numerous active compounds in MP might provide a synergistic effect and potentially offer other health benefits than those already identified and known. AIM OF THE STUDY: This study aimed to use a computational target fishing approach to predict the possible therapeutic effect of Marantodes pumilum and evaluated their effectivity. MATERIALS AND METHODS: This study involves a computational approach to identify the potential targets by using target fishing. Several databases were used: PubChem database to obtain the chemical structure of interested compounds; Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) server and the SWISSADME web tool to identify and select the compounds having drug-likeness properties; PharmMapper was used to identify top ten target protein of the selected compounds and Online Mendelian Inheritance in Man (OMIM) was used to predict human genetic problems; the gene id of top-10 proteins was obtained from UniProtKB to be analyzed by using GeneMANIA server to check the genes' function and their co-expression; Gene Pathway established by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) of the selected targets were analyzed by using EnrichR server and confirmed by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) version 6.8 and STRING database. All the interaction data was analyzed by Cytoscape version 3.7.2 software. The protein structure of most putative proteins was obtained from the RCSB protein data bank. Thedocking analysis was conducted using PyRx biological software v0.8 and illustrated by BIOVIA Discovery Studio Visualizer version 20.1.0. As a preliminary evaluation, a cell viability assay using Sulforhodamine B was conducted to evaluate the potential of the predicted therapeutic effect. RESULTS: It was found that four studied compounds are highly correlated with three proteins: EFGR, CDK2, and ESR1. These proteins are highly associated with cancer pathways, especially breast cancer and prostate cancer. Qualitatively, cell proliferation assay conducted shown that the extract has IC50 of 88.69 µg/ml against MCF-7 and 66.51 µg/ml against MDA-MB-231. CONCLUSIONS: Natural herbs are one of the most common forms of complementary and alternative medicine, and they play an important role in disease treatment. The results of this study show that in addition to being used traditionally to maintain women's health, the use of Marantodes pumilum indirectly has the potential to protect against the development of cancer cells, especially breast cancer. Therefore, further research is necessary to confirm the potential of this plant to be used in the development of anti-cancer drugs, especially for breast cancer.

Bioguided isolation of a selective compound from Calea phyllolepis leaves against breast cancer cells.

Plants of the Calea genus have been reported to contain lipophilic compounds, such as sesquiterpene lactones, with cytotoxic effect against different cancer cell lines. The aim of this manuscript was to investigate the chemical profile and cytotoxic activity of different fractions from Calea phylolepis leaves on different human cancer cell lines. The fractions were prepared using solvent extraction of increasing polarity, yielding hexane, ethyl acetate and methanolic fractions. All fractions were chemically analysed by thin layer chromatography (TLC), and their cytotoxic activity against HT-29 (colon adenocarcinoma), MCF-7 (breast cancer), U-251MG (malignant glioblastoma) and L929 (mouse fibroblast) cell lines was investigated. Among these, the hexane and ethyl acetate fractions showed higher cytotoxic effects, while the methanolic fraction did not show any cytotoxic effects. The major bioactive compound from the hexane fraction (12.15%) was isolated using chromatographic methods and was identified by nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS) analysis as 6-epi-ß-verbesinol coumarate. This compound showed activity against breast cancer cells (IC50 = 5.8 ± 1.0 µg/ml), similar to etoposide. Furthermore, 6-epi-ß-verbesinol coumarate showed low cytotoxicity to normal fibroblast cells, suggesting a high selectivity index (SI = 7.39) against breast cancer cells.

A new discovery: Total Bupleurum saponin extracts can inhibit the proliferation and induce apoptosis of colon cancer cells by regulating the PI3K/Akt/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC has a history of using herb in China for more than 2000 years, which can be traced back to the Classic of Shennong Materia Medica in the Han Dynasty. Although Saikosaponin, the main active ingredient of Bupleurum, has the effects of anti-tumor, yet we still do not know the mechanism by total Bupleurum saponin extracts (TBSE) produces this effect on colon cancer. AIM OF THE STUDY: It is predicted by network pharmacology that TBSE may play an anti-colon cancer role by regulating the PI3K-Akt-mTOR pathway. The purpose of this study is to investigate whether TBSE inhibits proliferation and promote apoptosis of colon cancer cells by regulating PI3K/Akt/mTOR pathway. MATERIALS AND METHODS: The effect of saikosaponins on the proliferation of SW480 and SW620 cells was detected by CCK-8, apoptosis was determined by flow cytometry, morphological changes of cells were observed by microscope, nuclear morphological changes were observed after immunofluorescence staining, the expression of apoptosis-related proteins Bax, Bcl2, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9 were detected by Western Blot, and the expression of apoptosis-related genes Bax, Bcl2, Caspase3 and Caspase9 were detected by RT-PCR. According to the theory of network pharmacology, the potential targets of saikosaponins and colon cancer were predicted by database Pharmmapper and Genecards database respectively. The intersection of saikosaponins and colon cancer was enriched and analyzed on the Metascape platform. Then, the expression of PI3K/Akt/mTOR pathway related protein PI3K, Akt, Mtor, p-PI3K, p-Akt, p-mTOR were detected by Western Blot, and the corresponding amount of RNA expressions in the pathway was confirmed by RT-PCR. RESULTS: The results of CCK-8 demonstrated that the survival rate of SW480 and SW620 cells decreased significantly when the concentration of TBSE was in the range of 25-200 µg/ml. The morphological observation showed that the cells lost normal cell morphology, cytoplasmic condensation, and partial loss of adhesion after treatment with TBSE. Flow cytometry indicated that the apoptosis rates of SW480 cells and SW620 cells treated with TBSE (50 µg/ml) were 48.47% ± 1.20% and 36.13% ± 1.76%, respectively. Western Blot firstly confirmed that TBSE significantly up-regulated the expression of pro-apoptotic proteins Bax, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and down-regulated the expression of anti-apoptotic protein Bcl2. And RT-PCR results implied that TBSE significantly up-regulated the gene expression of apoptotic factors Bax, Caspase3 and Caspase9, and significantly decreased the gene expression of Bcl2. It was predicted that the PI3K/Akt/mTOR pathway may be the main regulatory object of the antitumor effect of TBSE by network pharmacology. Subsequent WB experiment also revealed that TBSE could significantly down-regulate (P < 0.01) the expressions of PI3K, Akt, mTOR and phosphorylated proteins P-PI3K, P-Akt, P-MTOR. Meanwhile, RT-PCR results also indicated that TBSE could significantly down-regulate (P < 0.01) the gene expression levels of PI3K, Akt and mTOR. CONCLUSIONS: TBSE activated Bax/Bcl2 and caspase-9/caspase-3 cascade to induced apoptosis of human colon cancer SW480 and SW60 cells in a dose-dependent manner, which was obviously related to the inhibition of PI3K/Akt/mTOR signaling pathway.

The anti-tumor effect of OP-B on ovarian cancer in vitro and in vivo, and its mechanism: An investigation using network pharmacology-based analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Maidong (Liliaceae) is used as a yin-nourishing medication for the treatment of cardiovascular disease, inflammation, and assistant cancer chemotherapy in the clinic. Ophiopogonin B (OP-B), a major saponin extracted from Maidong, is reported to have potential antitumor activities against various human cancers. However, the effects of OP-B on human ovarian cancer (OC) and the potential mechanisms of action are yet elusive. AIM OF THE STUDY: In this study, we aimed to explore the potential molecular mechanisms of OP-B in the treatment of OC using network pharmacology. In vivo and in vitro experiments were conducted to further verify the therapeutic effects of OP-B on OC. MATERIALS AND METHODS: To investigate the functions of OP-B against OC holistically, the related targets of OP-B and OC were each predicted based on four public databases. Subsequently, the identified PPI network was constructed to detect the hub potential targets. In addition, GO and KEGG enrichment analysis were applied by Metascape database. Furthermore, we simultaneously investigated the anticancer effects of OP-B on SKOV3 and A2780 human ovarian cancer cells using a cell viability assay, transwell assay, and an image-based cytometric assay. The quantitative real-time PCR and western-blot assay were used to validate the RNA and protein levels of target genes in OP-B treated OC cells. At last, SKOV3-bearing BALB/c nude mice were applied to observe the effectiveness and toxicity of OP-B. RESULTS: Through network pharmacological analysis, OP-B was found to play a critical role in OC via multiple targets and pathways, especially the STAT3 signaling pathways. In addition, in vitro experiments found OP-B suppressed SKOV3 and A2780 cells proliferation in a time and concentration dependent manner, and markedly impaired cancer cell migration. Flow cytometry analysis revealed that OP-B significantly increased early and late apoptosis, induced G2/M phase cell cycle arrest in SKOV3 cells and G0/G1 phase cell cycle arrest in A2780 cells. Moreover, OP-B administration down-regulated the expression of p-STAT3 protein, whereas the RNA expression and total protein levels of STAT3 were not altered. Finally, in vivo experiments confirmed the therapeutic effects of OP-B on OC in nude mice with low toxicity in heart, liver, lung, and kidney. CONCLUSION: OP-B could efficiently suppress OC cellular proliferation, migration and induce apoptosis, cell cycle arrest mainly via the regulation of STAT3 signaling pathway. This study provides a promising potential application for an alternative to chemotherapy in ovarian cancer.

A novel strategy to reveal clinical advantages and molecular mechanism of aidi injection in the treatment of pancreatic cancer based on network meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pancreatic cancer is a common malignancy worldwide due to its poor prognosis and high mortality rate. It is clinically proven that the combination of chemotherapeutic drugs and Traditional Chinese Medicine injections (TCMIs) significantly improves the therapeutic effect. AIM OF THE STUDY: To evaluate the efficacy and clinical benefits of TCMIs in combination with chemotherapy in the treatment of pancreatic cancer and to explore the mechanism of clinical advantage of Aidi injection. METHODS: Randomized controlled trials (RCTs) were searched in databases by NMA before December 29, 2020. WinBUGS 1.4, Stata 14.0, and R 4.0.4 software were used for calculations. All results were expressed as odds ratios and 95% credible intervals. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. And then, biological experiments were integrated to verify the results of network pharmacology analysis. (PROSPERO ID: CRD42021283559). RESULTS: A total of 33 RCTs with 8 TCMIs and 2011 patients were included. The results of NMA showed that Aidi injection can significantly improve the clinical efficacy (OR = 0.34, 95%CI: 0.16-0.74), and the clinical advantage was that it can significantly alleviate the leukopenia and thrombocytopenia caused by chemotherapy (OR = 5.65, 95%CI: 1.18-28.13). A total of 23 chemical compounds and 280 potential targets for Aidi injection were obtained from the online databases. Among them, there were 22 compounds, 50 targets and 211 signaling pathways closely related to leukopenia. Five genes were predicted to be core targets of ADI in alleviating leukopenia, and 2 of them (TP53 and VEGFA) were confirmed by biological experiments as regulatory targets of ADI in the treatment of PC. CONCLUSIONS: In conclusion, TCMIs in combination with chemotherapy, can improve clinical efficacy and safety in the treatment of pancreatic cancer. However, the overall evidence base is low, and large samples with multi-center RCTs are still needed to support further research findings. Aidi injection can alleviate leukopenia mainly by intervening in oxidative stress, regulating cell proliferation and apoptosis, and regulating the inflammatory response. The combined application of NMA, network pharmacology, and biological experiments provides a reference for clinical evaluation and mechanism of action exploration of other drugs.

Ethnopharmacological nexus between the traditional Thai medicine theory and biologically based cancer treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: The two major theories utilized for diagnosis and treatment in Traditional Thai Medicine (TTM) are the Four Element Theory and the Herbal Flavor Theory. A TTM "Poh-Pu" Remedy has been effectively utilized in Thailand for cancer therapy for centuries. AIMS OF STUDY: To investigate anti-inflammatory activity and liver cancer cytotoxicity of Poh-Pu remedy. To determine relationships between the TTM Herbal Flavor theory and the Four Element theory and total flavonoid content and biological activities of Poh-Pu Remedy plant extracts. MATERIALS AND METHODS: Each plant ingredient was macerated with 95% ethanol. The extracts were investigated for cytotoxic activity against liver cancer using a sulforhodamine B assay, and anti-inflammatory activity was evaluated by inhibition of nitric oxide production. The total flavonoid content was determined by an aluminum chloride colorimetric assay. The relationships between the TTM theories, total flavonoid content, and biological activities were evaluated by correlation and cluster analysis. RESULTS: Mammea siamensis exerted potent cytotoxicity against hepatocellular carcinoma (HepG2) cell lines with an IC50 of 3.15 ± 0.16 µg/mL and low cytotoxicity to the non-cancerous cells (HaCat) with an IC50 33.39 ± 0.40 µg/mL (Selective index (SI) = 10.6). Tiliacora triandra was selectively cytotoxic to cholangiocarcinama (KKU-M156) cells with an IC50 of 12.65 ± 0.92 µg/mL (SI = 6.4). Curcuma comosa was the most potent anti-inflammatory inhibitor of nitric oxide production with an IC50 of 2.75 ± 0.34 µg/mL. Campomanesia aromatica exhibited the highest total flavonoid content of 259.7 ± 3.21 mg quercetin equivalent/g. Pungent plants were most prevalent in the TTM remedy. CONCLUSION: Pungent, fragrant, bitter and nauseating plants utilized in TTM cancer remedy were successfully investigated and identified several lead plants and components with cytotoxic and antiinflammatory activity that require further study. The TTM wind element theory appeared to be aligned with cancer-related activity. Biological activity results of taste from herbs related with The TTM Herbal Flavor theory. The extra-oral locations of flavor receptors are a promising target for biological activity of TTM which require further scrutiny and identified several lead plants and components with cytotoxic and antiinflammatory activities that also require further study.

Antibacterial and cytotoxicity evaluation of Arum hygrophilum Bioss.

OBJECTIVE: Arum hygrophilum Bioss is a plant native to Asia, Europe, and Northern Africa. It is consumed as beverages, spices, or cooked leaves to cure gastrointestinal infections and cancer. This study aims to determine the antibacterial and anticancer effectivenesss of A. hygrophilum Bioss. MATERIALS AND METHODS: Using the well-diffusion method, the antimicrobial activity of the plant's aqueous extract and five other organic extracts were evaluated against bacteria often associated with food poisoning. The assessment of the antiproliferative activity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was done on five cancerous cell lines and on fibroblasts as a reference cell line. RESULTS: The growth of L. monocytogenes was significantly inhibited by the aqueous and ethanolic extracts. Both extracts had a minimum inhibitory concentration (MIC) of 62.5 mg/mL. The inhibition caused by the methanolic extract had a MIC of 500 mg/mL. The growth of S. aureus and MRSA were inhibited by the aqueous extract with a MIC of 500 mg/mL, while the inhibition caused by the ethanolic extract had a MIC of 250 mg/mL on MRSA and 500 mg/mL on S.aureus. Both strains of S.aureus were also inhibited by the 3-pentanon extract, while the butanol extract only exhibited a moderate growth inhibition against MRSA. The MTT assay showed that the aqueous extract had not affected the proliferation of cancer cell lines. The cytotoxicity of the ethanolic and methanolic extracts had no concentration-inhibition relationship and the IC50 values were above 800 µg/mL for all extracts. CONCLUSIONS: L. monocytogenes, S. aureus, and methicillin-resistant Staphylococcus aureus (MRSA) were inhibited by different Arum extracts. The antibacterial activity of Arum hygrophilum Bioss against foodborne pathogens makes it safe to use as a natural food preservative, and as a source for sanitizers and antimicrobials. Further investigation is recommended to determine the cytotoxicity of the plant against additional cancer cell lines.

Effect of cyanide ions (CN-) extracted from cassava (Manihotesculenta Crantz) on Alveolar Epithelial Cells (A549 cells).

Cassava (Manihotesculenta Crantz) is one of the most important root crops in tropical countries. It is a major source of cyanogenic glycosides viz. linamarin and lotaustralin, and these on breakdown liberate HCN and ketone. Cassava cyanide extract (CCE) from cassava leaves and tuber rinds were formulated as a biopesticide against certain borer insect pests of horticultural crops. Adenocarcinomic human alveolar basal epithelial cells (A549) were treated with three different concentrations (100, 200, 400 ppm) of CCE. The MTT and NRU assays showed dose-dependent cytotoxicity. The DCFH-DA assay does not show any free radical scavenging activity, whereas the NRR assay showed a reduction in the nitrile radicals with an increase in the concentration of the bioactive compound. A negative correlation was found between the concentration of the bioactive principles and mitochondrial and lysosomal functions. Various cellular assays demonstrated the cellular response of the CCE, and it was found that at higher concentration (400 ppm), the CCE exert a significant necrotic cell death rather than apoptosis. The results of the study indicated that the CCE have a remarkable tendency of anti-proliferative ability.

Astragalus polysacharin inhibits hepatocellular carcinoma-like phenotypes in a murine HCC model through repression of M2 polarization of tumour-associated macrophages.

CONTEXT: Astragalus polysaccharin (APS), an extract of Astragalus propinquus Schischk, exerts antitumor effects in hepatocellular carcinoma (HCC). OBJECTIVE: This study investigated the mechanism of action of APS in HCC. MATERIALS AND METHODS: Tumour-associated macrophages (TAMs) were treated with APS (0, 8, 16 mg/mL) for 24 h. APS (16 mg/mL)-treated TAMs were co-cultured with MHCC97H/Huh7 cells for 24 h. Finally, BALB/c nude mice were divided into PBS, APS (50 mg/kg), APS (100 mg/kg), APS (200 mg/kg) groups: mice were inoculated with Huh7 cells to construct tumour xenograft model, followed by administration of APS (50, 100, 200 mg/kg) or PBS daily for 30 days. Cell proliferation, migration, invasion, tumour growth, macrophage markers and proportions were measured. RESULTS: APS 16 mg/mL treatment enhanced the expression of M1 macrophage markers (iNOS, IL-1ß and TNF-α) and M1 macrophage proportions, while reducing the expression of M2 macrophage markers (IL-10, Arg-1) and M2 macrophage proportions in TAMs. Moreover, the APS-mediated M1 phenotype of TAMs significantly repressed cell proliferation, migration and invasion of MHCC97H and Huh7 cells. Moreover, APS (50, 100, 200 mg/kg) enhanced M1 macrophage proportions and reduced M2 macrophage proportions in the tumour tissues, and thus inhibited tumour growth of HCC. DISCUSSION AND CONCLUSIONS: APS inhibits HCC-like phenotypes in a murine HCC model through repression of M2 polarization of TAMs. This work provides a novel theoretical basis for the application of APS in the clinical treatment of HCC.

Novel Anti-Tubulin Compounds from Trigonella foenum-graecum Seeds; Insights into In-vitro and Molecular Docking Studies.

BACKGROUND: Fenugreek, also known as Trigonella foenum-graecum L, is a natural plant that belongs to the Fabaceae family and has been known as a promising source of bioactive compounds. It has been widely used as traditional medicine since it has shown to lower blood glucose, manage cholesterol levels and further aid in the prevention and treatment of cancer. Herein, we aim to evaluate the anticancer activity of methanolic fenugreek seed extract against several cancer cell lines. METHODS: We sought to investigate the phytochemical classes present in multiple fenugreek seeds extracts using HPLC-DAD followed by LC/MS, predict and investigate anticancer activity using PASS online webserver, the CellTiter-Glo assay, evaluate ADME properties, and perform molecular docking for all bioactive compounds via Maestro software. RESULTS: Multiple extracts exhibited distinct phytochemical classes that demonstrated different biological activities. Fenugreek methanolic extract contains flavonoid chemical class, which showed the highest anticancer activity against the HCT8 cell line of colorectal cancer (IC50 of 8.83 µg/mL), followed by KAIMRC1 breast cancer cell line (IC50 of 35.06 µg/mL), HL60 leukemia cell line (37.80 µg/mL), MDA-MB-231 breast cancer cell line (38.51 µg/mL), and lastly, HCT116 colorectal cancer cell line with IC50 of 56.03 µg/mL. In contrast, the chloroform extract was inactive. The molecular docking study for all the bioactive compounds suggested that flavonoids F6 (-9.713 and -12.132), F7 (-10.166 and -12.411), and F11 (-10.084 and -13.516) possess the highest docking scores through SP and XP scores, respectively. CONCLUSION: The obtained results confirm that the bioactive compounds present in fenugreek seeds exhibit anticancer activity against several cancer cells that can mediate via tubulin polymerization inhibition. Although our study has evaluated the anticancer potential of Trigonella foenum-graecum as a promising natural source for new anticancer agents, fenugreek biological activity needs further research and investigations on their mechanism of action and toxicity profile.

Goshajinkigan attenuates paclitaxel-induced neuropathic pain via cortical astrocytes.

The anticancer agents platinum derivatives and taxanes such as paclitaxel (PCX) often cause neuropathy known as chemotherapy-induced peripheral neuropathy with high frequency. However, the cellular and molecular mechanisms underlying such neuropathy largely remain unknown. Here, we show new findings that the effect of Goshajinkigan (GJG), a Japanese KAMPO medicine, inhibits PCX-induced neuropathy by acting on astrocytes. The administration of PCX in mice caused the sustained neuropathy lasting at least 4 weeks, which included mechanical allodynia and thermal hyperalgesia but not cold allodynia. PCX-evoked pain behaviors were associated with the sensitization of all primary afferent fibers. PCX did not activate microglia or astrocytes in the spinal cord. However, it significantly activated astrocytes in the primary sensory (S1) cortex without affecting S1 microglial activation there. GJG significantly inhibited the PCX-induced mechanical allodynia by 50% and thermal hyperalgesia by 90%, which was in accordance with the abolishment of astrocytic activation in the S1 cortex. Finally, the inhibition of S1 astrocytes by an astrocyte-toxin L-alpha-aminoadipic acid abolished the PCX-induced neuropathy. Our findings suggest that astrocytes in the S1 cortex would play an important role in the pathogenesis of PCX-induced neuropathy and are a potential target for its treatment.

Tackling of Renal Carcinogenesis in Wistar Rats by Silybum marianum Total Extract, Silymarin, and Silibinin via Modulation of Oxidative Stress, Apoptosis, Nrf2, PPARγ, NF-κB, and PI3K/Akt Signaling Pathways.

The present work was designed to assess the efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally induced renal carcinogenesis in male Wistar rats and their roles in regulating oxidative stress, inflammation, apoptosis, and carcinogenesis. The diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4)-administered rats were orally treated with STE (200 mg/kg b.w.), Sm (150 mg/kg b.w.), and Sb (5 mg/kg b.w.) every other day either from the 1st week or from the 16th week of carcinogen administration to the end of 25th week. The treatments with STE, Sm, and Sb attenuated markers of toxicity in serum, decreased kidney lipid peroxidation (LPO), and significantly reinforced the renal antioxidant armory. The biochemical results were further confirmed by the histopathological alterations. The treatments also led to suppression of proinflammatory mediators such as NF-κß, p65, Iκßα, and IL-6 in association with inhibition of the PI3K/Akt pathway. Furthermore, they activated the expressions of PPARs, Nrf2, and IL-4 in addition to downregulation of apoptotic proteins p53 and caspase-3 and upregulation of antiapoptotic mediator Bcl-2. The obtained data supply potent proof for the efficacy of STE, Sm, and Sb to counteract renal carcinogenesis via alteration of varied molecular pathways.

Sage, Salvia officinalis L., Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis.

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils' yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, ß-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs' essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.