Cytotoxic Properties on Cervical and Liver Cancer Cells of Two Plant Recipes from Burkina Faso

Cancer is one of the deadliest diseases in developing countries. In recent years, natural plant-based compounds have been used in the search for drugs to combat numerous diseases, including cancer. In this study, we evaluate the cytotoxic properties of paanfo tiben 1 and paanfo tiben 2, two traditional herbal formulations from Burkina Faso used in the treatment of cancer in Burkina Faso. To this end, the recipes were infused and freeze-dried. The dry extracts obtained were used to determine total phenolics and flavonoids content, assess antioxidant activity using the DPPH, ABTS and FRAP methods, evaluate anti-inflammatory properties by inhibiting 15-LOX, COX 1 and 2, and assess cytotoxic activity on HeLa cervical cancer and HePG2 liver cancer cell lines using the MTT test. The paanfo tiben 1 recipe showed the highest levels of total phenolics and flavonoids, as well as the best antioxidant activities, with IC50 values of 21.020 ± 0.6 µg/ml and 22.94 ± 0.57 µg/ml for DPPH and ABTS, and 165.15 mM EAA/mg dry extract for FRAP. It also exhibited the best cytotoxic activity with IC50 values of 112.02 ± 0.025 µg/ml on HeLa cells and 80.67 ± 6.08 µg/ml on HepG2 cells. On the other hand, paanfo tiben 2 exhibited the best anti-inflammatory activities through inhibition of 15-LOX and COX 1, with inhibition percentages at 100 µg/ml of 32.523% and 24.717 % respectively. These results could justify the traditional use of these two recipes by traditional health practitioners in the treatment of cancer sufferers in Burkina Faso.

Antibacterial mechanism with consequent cytotoxicity of different reinforcements in biodegradable magnesium and zinc alloys: A review

Benefits achieved by the biodegradable magnesium(Mg) and zinc(Zn) implants could be suppressed due to the invasion of infectious microbial, common bacteria, and fungi. Postoperative medications and the antibacterial properties of pure Mg and Zn are insufficient against biofilm and antibiotic-resistant bacteria, bringing osteomyelitis, necrosis, and even death. This study evaluates the antibacterial performance of biodegradable Mg and Zn alloys of different reinforcements, including silver(Ag), copper(Cu), lithium(Li), and gallium(Ga). Copper ions(Cu^(2+)) can eradicate biofilms and antibiotic-resistant bacteria by extracting electrons from the cellular structure. Silver ion(Ag^(+)) kills bacteria by creating bonds with the thiol group. Gallium ion(Ga^(3+)) inhibits ferric ion(Fe^(3+)) absorption, leading to nutrient deficiency and bacterial death. Nanoparticles and reactive oxygen species(ROS) can penetrate bacteria cell walls directly, develop bonds with receptors, and damage nucleotides. Antibacterial action depends on the alkali nature of metal ions and their degradation rate, which often causes cytotoxicity in living cells. Therefore, this review emphasizes the insight into degradation rate, antibacterial mechanism, and their consequent cytotoxicity and observes the correlation between antibacterial performance and oxidation number of metal ions.

Echinoside A from Pearsonothuria graeffei Exert the Cytotoxicity to MDA-MB-231 Cells via Mitochondrial Membrane and Modulation of PI3K/Akt/mTOR Pathway

A kind of triterpene glycosides echinoside A(EA)was extracted from sea cucumber Pearsonothuria graeffei,and its yield was about 0.78%.The purity of EA was 99.0%,and its molecular weight was 1206 Da.EA was a linear tetrasaccharide attached to a pentacyclic triterpene aglycon.It inhibited the growth of MDA-MB-231 cells in vitro.The antitumor effect was related to elevate ROS level,decrease mitochondrial membrane potential,enhance caspase-3 expression,induce cells apoptosis and arrest cell cycle at G2/M phase.EA also dose-dependently suppressed the expressions of phophorylation proteins p-PI3K,p-Akt,and p-mTOR as analyzed by western blotting.These results suggested that EA caused MDA-MB-231 cells apoptosis via intrinsic mitochondrial and PI3K/Akt/mTOR pathway.EA can be a potential anti-breast cancer agent to enhance the clinical efficacy.

Evaluation of cytotoxic and anti-tumor activity of partially purified serine protease isolate from the Indian earthworm Pheretima posthuma

Objective:To isolate,partially purify and evaluate the cytotoxic and antitumor activity of a serine protease from the chosen Indian earthworm Pheretima posthuma.Methods:Whole animal extract was prepared and purified its protein constituents by size and charge based chromatographic separation techniques using Sephadex G-50 and DEAE-Cellulose resin respectively.Average molecular weight of the protein isolate was determined and analyzed for its cytotoxic property against Vero cells in different dilutions(1:20 and 1:40)and anti-tumor activity by MTT assay(a colorimetric assay)using breast cancer cell line MCF-7,with tamoxifen as standard.Results:One of the protein constituents after purification was characterized as serine protease by Caseinolytic plate diffusion assay.Average molecular weight of this purified isolate was determined,by SDS-PAGE analysis with standard protein ladder,as of 15 kDa.The performed tests suggested that the 15kDa fraction has potent cytotoxic activity and satisfactory antitumor activity as well in vitro.Conclusions:Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction.Further investigation into the mechanism(s)of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.

Cytotoxic phenazine and antiallergic phenoxazine alkaloids from an arctic Nocardiopsis dassonvillei SCSIO 502F

Microbes well-adapted to the Arctic Ocean are promising for producing novel compounds,due to their fancy strategies for adaptation and being under-investigated.Two new phenazine alkaloids(1 and 2)and one new phenoxa-zine(3)were isolated from Nocardiopsis dassonvillei 502F,a strain originally isolated from Arctic deep-sea sediments.AntiSMASH analysis of the genome of Nocardiopsis dassonvillei 502F revealed the presence of 16 putative biosynthetic gene clusters(BGCs),including a phenazine BGC.Most of the isolated compounds were evaluated for their antibacterial,antiallergic,and cytotoxic activities.Among them,compounds 4 and 5 exhibited potent in vitro cytotoxic activities against osteosarcoma cell line 143B with IC_(50) values 0.16 and 20.0μM,respectively.Besides,the results of antiallergic activities of compounds 6-8 exhibited inhibitory activities with IC_(50) values of 10.88±3.05,38.88±3.29,and 2.44±0.17μg/mL,respectively(IC_(50)91.6μM for the positive control loratadine).

New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

Two novel compounds including a cyclohelminthol type polyketide(namely oxaleimide K,1)and a maleimide deriva-tive(namely peniroquefortine A,2),and a new natural product(namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide,3),together with four known compounds(4-7),were isolated and identified from fungus Penicillium roqueforti,which was separated from the root soil of Hypericum beanii N.Robson collected from the Shennongjia For-estry District,Hubei Province.Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment.Compound 1 represents the second example of a cyclohelminthol type polyketide,which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin(oct-1-en-3-yl)moiety,and compound 2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds.Remarkably,the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound 1 is determined by the single-crystal diffraction analysis for the first time,highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydro-furan moiety for 1 rather than a Z-configuration as previously reported in the biosynthesis study,which gives a new insight into the structural elucidation of this category of polyketides.Additionally,compound 1 exhibited significant cytotoxic activity against multiple tumor cells,especially against the Farage and SU-DHL-2 cells(IC_(50)<20μM,48 h).Further mechanism study revealed that compound 1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.

Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Anti-Tumor and Anti-Diabetic Effects of Sarsasapogenin

In this paper,the pharmacological effects and molecular mechanisms of sarsasapogenin,such as anti-oxidant,anti-inflammatory and anti-diabetic effects,are reviewed in order to provide a theoretical basis for the subsequent development and clinical application of sarsasapogenin.

Preparation of kakkatin derivatives and their anti-tumor activity

BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and inflammation.Kakkatin is an isoflavone polyphenolic compound isolated from PF flower.However,the effect of kakkatin and its derivatives on anti-tumor has not been well explored.AIM To design and synthesize a kakkatin derivative[6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one(HK)]to explore its anti-tumor biological activity.METHODS Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol,and the derivative of kakkatin was prepared;the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability,a clone formation assay was adopted to detect cell proliferation,apoptosis,necrosis,and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry.Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay.The potential mechanism of HK on hepatocellular carcinoma(HCC)SMMC-7721 cells was explored through network pharmacology and molecular docking,and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK.RESULTS Compared with kakkatin,the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells,but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times,with an IC50 value of 2.5μM,and the tumor inhibition effect was better than cisplatin,which could significantly inhibit the cloning,invasion and metastasis of HCC SMMC-7721 cells,and induce apoptosis and G2/M cycle arrest.Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway.CONCLUSION HK have a significant inhibitory effect on HCC SMMC-7721 cells,and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway,making it a good lead drug for the treatment of HCC.

Mechanism of Anti-tumor Effects of Viola Medicinal Materials Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.

Advances in Research of Anti-tumor Effect of Aconiti Radix

In this paper,the anti-tumor effects of Aconiti Radix were reviewed and summarized,and the clinical feasibility of Aconiti Radix as a potential anti-tumor drug was analyzed,in order to provide a useful reference for the future research and development of new anti-cancer drugs of Aconiti Radix.

Screening for Anti-tumor Activity of Fractions from Buddleja officinalis Maxim

[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.

Treatment of primary nasal tuberculosis with anti-tumor necrosis factor immunotherapy:A case report

BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.

Research progress on the anti-tumor effect of Codonopsis pilosula

Currently,the mortality rate of malignant tumors ranks second globally,surpassed only by cardiovascular and cerebrovascular diseases.The treatment of malignant tumors poses a formidable challenge to both modern medicine and traditional Chinese medicine(TCM).To date,TCM has developed a substantial foundational theoretical understanding and accumulated significant clinical experience in combating tumors.According to TCM foundational theories,"Qi deficiency"is a critical symptom associated with cancer,and"fortifying the body's vitality while expelling pathogens"is the cornerstone of TCM's approach to tumor treatment and bodily balance.Codonopsis pilosula(CP),a Qi-invigorating herb,is known to invigorat the spleen,benefit the lungs,nourish the blood,and promote bodily fluids.It is often employed as a substitute for ginseng in clinical settings.Prolonged clinical observations have identified key active constituents of CP,such as Codonopsis polysaccharides,isoimperatorin,saponins,lobetyolin,sesquiterpene lactones,and muscone.These ingredients exhibit various therapeutic properties,including anti-tumor,immunomodulatory,anti-infective,antioxidant,and hematopoiesis-enhancing effects.Additionally,when CP is combined with other TCM herbs like Astragalus and Atractylodes macrocephala,it bolsters the body's vital energy and rejuvenates both Qi and blood.CP can be used in combination with chemotherapy agents to mitigate the adverse effects of radiotherapy and chemotherapy.Moreover,CP demonstrates potential in preventing precancerous lesions.This review summarizes recent research findings on the anti-tumor properties of CP,elucidates the anti-tumor effects and molecular mechanisms of its active components,provides a basis for promoting the utilization of CP resources and its active constituents,and offers insights for the research and development of new anti-tumor drugs.

A new cytotoxic 2-(2-phenylethyl)chromone from Chinese eaglewood

A new compound 8-chloro-5,6,7-trihydroxy-2-（3-hydroxy-4-methoxyphenethyl）-5,6,7,8-tetralaydro-4H-chromen-4-one （1） was isolated from the Chinese eaglewood [Aquilaria sinensis （Lour.） Gilg]. Its structure was elucidated on the basis of spectral data. Compound I showed cytotoxicity against human gastric cancer cell line （SGC-7901） in vitro by MTT method with the IC50 value of 14.6 μg/mL.

Chronic toxicity and cytotoxicity of synthetic pyrethroid insecticide cis-bifenthrin

With the increasing use of synthetic pyrethroids （SPs）, the significance of ecological safety and health risk is an emerging concern, In this study, we evaluated the chronic aquatic toxicity of eis-bifenthrin （cis-BF） in Daphnia magna and its cytotoxicity in Chinese hamster ovary （CHO） cells as well as human cervical carcinoma （Hela） ceils. Chronic aquatic toxicity tests showed that cis-BF could significantly affect the reproduction of D. magna. The lowest observed effective concentration and the non-observed effective concentration of cis-BF to D. magna were 0.02 and 0.01 μg/L, respectively, and the chronic value was 0.014 μg/L. The intrinsic rate of natural increase was significantly decreased （p 〈 0.05） to 0.02 μg/L. The cytotoxicity assay demonstrated that cis-BF decreased cell viability in CHO and Hela cells in a concentration- and time-dependent manner. The IC50 values for Hela and CHO cells were 4.0 × 10^-5 and 3.2 × 10^-5 mol/L, respectively. Together, these results indicated that cis-BF induced chronic toxicity in both aquatic invertebrate animals and mammalian cells. These findings assist in understanding the impact of SPs on health and environmental safety. Considering the wide spectrum of SPs, a more comprehensive understanding of the negative effects is indispensible for planning future application and regulation of these pesticides.

A cytotoxic compound from the leaves of Juglans mandshurica

From Juglans mandshurica leaves, a new quinone compound was isolated through bioassay-guided fractionation. The structure elucidation of the compound was established based on spectroscopic studies, notably of the 2D NMR spectra. The compound exhibited moderate cytotoxic activities against Hela, MCF-7, BGC823 and 3T3-Llcell lines with IC50 ranges from 7.5 to 26.8 μmol/L.

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.