Anticancer Potential of ß-Carboline Alkaloids: An Updated Mechanistic Overview.

his comprehensive review is designed to evaluate the anticancer properties of ß-carbolines derived from medicinal plants, with the ultimate goal of assessing their suitability and potential in cancer treatment, management, and prevention. An exhaustive literature survey was conducted on a wide array of ß-carbolines including, but not limited to, harmaline, harmine, harmicine, harman, harmol, harmalol, pinoline, tetrahydroharmine, tryptoline, cordysinin C, cordysinin D, norharmane, and perlolyrine. Various analytical techniques were employed to identify and screen these compounds, followed by a detailed analysis of their anticancer mechanisms. Natural ß-carbolines such as harmaline and harmine have shown promising inhibitory effects on the growth of cancer cells, as evidenced by multiple in vitro and in vivo studies. Synthetically derived ß-carbolines also displayed noteworthy anticancer, neuroprotective, and cognitive-enhancing effects. The current body of research emphasizes the potential of ß-carbolines as a unique source of bioactive compounds for cancer treatment. The diverse range of ß-carbolines derived from medicinal plants can offer valuable insights into the development of new therapeutic strategies for cancer management and prevention.

Identification of a ß-Carboline Alkaloid from Chemoselectively Derived Vanilla Bean Extract and Its Prevention of Lipid Droplet Accumulation in Human Hepatocytes (HepG2).

Targeting bioactive compounds to prevent lipid droplet accumulation in the liver, we explored an antioxidative extract from vanilla bean (Vainilla planifolia) after chemo-selective derivatization through heating and acid modification. The chemical analysis of vanilla bean extract through chemoselective derivatization resulted in the identification of sixteen compounds (34-50) using LC-MS/MS analysis. A ß-carboline alkaloid with a piperidine C-ring and a vanillin moiety at C-1 (34) was identified by molecular networking and diagnostic fragmentation filtering approaches. ß-carboline alkaloid 34 exhibited significant inhibitory activity of lipid droplet accumulation (LDAI) in oleic acid-loaded hepatocellular carcinoma HepG2 cells. The LDAI activity was associated with both activation of lipolysis and suppression of lipogenesis in the cells. The study indicates that crude plant extracts, following chemoselective derivatization, may contain bioactive compounds that could be beneficial in preventing hepatosteatosis and could serve as a source of lead compounds for drug development. This approach may be useful to investigate other mixtures of natural products and food resources.

[Dumai moxibustion combined with low-dose tadalafil for erectile dysfunction: Evaluation of therapeutic effect].

OBJECTIVE: To investigate the clinical effect of dumai (governor meridian) moxibustion combined with low-dose tadalafil in the treatment of ED with decline of vital gate fire. METHODS: We enrolled in this study 130 ED patients with decline of vital gate fire who met the inclusion criteria and equally randomized them into a control and an experimental group, the former treated with low-dose tadalafil tablets at 5 mg once a day while the latter by dumai moxibustion once a week in addition, all for 4 weeks. Of the total number of subjects, 62 in the control group and 63 in the experimental group completed the experiment. We recorded the scores on IIEF-5, Erection Quality Scale (EQS), Erection Hardness Scale (EHS), TCM symptoms and Treatment Satisfaction Scale (TSS) as well as the penile hemodynamic parameters peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) before and after treatment and compared them between the two groups. RESULTS: The total response rate was significantly higher in the experimental group than in the control (87.30% vs 66.13%, P < 0.05). IIEF-5, EQS, EHS and TSS scores, PSV and RI were markedly increased while TCM symptoms and EDV remarkably decreased in both groups after treatment (P < 0.05), even more significantly in the experimental than in the control group (P < 0.05). CONCLUSION: Dumai moxibustion combined with low-dose tadalafil can improve erectile function, increase penile blood flow velocity and alleviate clinical symptoms in ED patients with decline of vital gate fire, with definite clinical effect and safety.

ß-Carboline Alkaloids in Soy Sauce and Inhibition of Monoamine Oxidase (MAO).

Monoamine oxidase (MAO) oxidizes neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines such as the MPTP neurotoxin. Its inhibitors are useful as antidepressants and neuroprotectants. This work shows that diluted soy sauce (1/3) and soy sauce extracts inhibited human MAO-A and -B isozymes in vitro, which were measured with a chromatographic assay to avoid interferences, and it suggests the presence of MAO inhibitors. Chromatographic and spectrometric studies showed the occurrence of the ß-carboline alkaloids harman and norharman in soy sauce extracts inhibiting MAO-A. Harman was isolated from soy sauce, and it was a potent and competitive inhibitor of MAO-A (0.4 µM, 44 % inhibition). The concentrations of harman and norharman were determined in commercial soy sauces, reaching 243 and 52 µg/L, respectively. Subsequently, the alkaloids 1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (THCA) and 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (MTCA) were identified and analyzed in soy sauces reaching concentrations of 69 and 448 mg/L, respectively. The results show that MTCA was a precursor of harman under oxidative and heating conditions, and soy sauces increased the amount of harman under those conditions. This work shows that soy sauce contains bioactive ß-carbolines and constitutes a dietary source of MAO-A and -B inhibitors.

ß-Carboline alkaloids from Picrasma quassioides and their 3D-QSAR study on anti-inflammation in LPS-induced RAW 264.7 cells.

Two new ß-carboline alkaloids (1-2), 1-pyrrolidone propionyl-ß-carboline (1) and 1-(3-hydroxy-2-oxopiperidine-1-ethyl)-4,8-dimethoxyl-ß-carboline (2), named kumujantine W and J respectively, together with ten known compounds (3-12) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated from spectral data including 1D and 2D NMR, UV, IR, HR-ESI-MS spectroscopic analysis and ECD calculations as well as by comparison to the reference databases or literature. The anti-inflammatory effects of these alkaloids (1-12) and six other ß-carboline alkaloids (13-18) in LPS-induced RAW 264.7 cells were evaluated by measuring nitric oxide (NO) concentrations. Among them, compounds 1, 3, 6, 15, and 17 could inhibit the secretion of NO, displaying significant anti-inflammatory activity without affecting cell viability in vitro, and 3D-QSAR analysis further revealed the influence of groups on the activity in ß-carboline alkaloids.

Computational Insights into ß-Carboline Inhibition of Monoamine Oxidase A.

Monoamine oxidases (MAOs) are an important group of enzymes involved in the degradation of neurotransmitters and their imbalanced mode of action may lead to the development of various neuropsychiatric or neurodegenerative disorders. In this work, we report the results of an in-depth computational study in which we performed a static and a dynamic analysis of a series of substituted ß-carboline natural products, found mainly in roasted coffee and tobacco smoke, that bind to the active site of the MAO-A isoform. By applying molecular docking in conjunction with structure-based pharmacophores and molecular dynamics simulations coupled with dynamic pharmacophores, we extensively investigated the geometric aspects of MAO-A binding. To gain insight into the energetics of binding, we used the linear interaction energy (LIE) method and determined the key anchors that allow productive ß-carboline binding to MAO-A. The results presented herein could be applied in the rational structure-based design and optimization of ß-carbolines towards preclinical candidates that would target the MAO-A enzyme and would be applicable especially in the treatment of mental disorders such as depression.

Evaluation of the In Vitro Wound-Healing Potential of Ayahuasca.

Ayahuasca is an Amazonian drink, which contains ß-carboline alkaloids and N,N-dimethyltryptamine. The aim of this study was to evaluate the healing potential of decoctions of a commercial mixture, four individual plants and four mixtures of two plants used in the ayahuasca preparation. Thus, the cytotoxic potential of the samples was evaluated and a wound-healing assay was performed with a NHDF cell line. Subsequently, a parallel artificial membrane permeability assay was also performed, to verify if any psychoactive compound could be absorbed by skin fibroblasts. The integrity and permeability of the cell layer were also evaluated, using the transepithelial electrical resistance assay and Lucifer yellow permeability assay, respectively. The compounds absorbed by the cell layer were quantified by high-performance liquid chromatography coupled to a diode array detector. The results showed that only one sample showed cytotoxicity and all the others promoted the migration of skin fibroblasts. Additionally, it was also verified that ß-carbolynic alkaloids and N,N-dimethyltriptamine were not absorbed by the cell layer, and in general, did not interfere with its permeability and integrity. To the best of our knowledge, this is the first study where ayahuasca's wound-healing potential was evaluated.

Phosphodiesterase-5 Inhibitory Activity of Canthin-6-One Alkaloids and the Roots of Eurycoma longifolia and Eurycoma harmandiana.

Eurycoma longifolia (EL) and Eurycoma harmandiana (EH) are natural medicinal plants belonging to the Simaroubaceae family, and are well-known for their ability to enhance male sexual performance. The present study investigated the phosphodiesterase-5 (PDE-5) inhibitory activity of intact roots of EL and EH. Additionally, canthin-6-one alkaloids, ß-carboline alkaloids, and quassinoids were also screened for PDE-5 inhibitory activity. We developed in vitro root and callus cultures of EL and EH to determine their PDE-5 inhibitory activity. Our results indicated that canthin-6-one alkaloids, which include canthin-6-one-9-O-ß-D-glucopyranoside, 9-methoxycanthin-6-one, canthin-6-one, and 9-hydroxycanthin-6-one, exhibited PDE-5 enzymatic inhibitory activity, with IC50 values of 2.86±0.23, 3.30±1.03, 4.31±0.52, and 4.66±1.13 µM, respectively. The ethanolic extract of the intact roots of EL and EH, and the in vitro root culture of EH had large amounts of canthin-6-one alkaloids (1.50±0.04, 2.12±0.03, and 3.48±0.08 mg/g dry weight, respectively), and showed potent PDE-5 inhibition. Our findings indicate that in vitro root cultures of EH may be used to replace intact plants, and canthin-6-one-9-O-ß-D-glucopyranoside should be further investigated for development as a health supplement.

Pharmacodynamics assessment of ß-carboline from the roots of Psammosilene tunicoides as analgesic compound.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Psammosilene tunicoides (W. C. Wu et C. Y. Wu) is a well-known medicinal herb for the treatment of pain, hemostasia and rheumatoid arthritis among Chinese people. AIM OF THE STUDY: The present study aimed to investigate the antinociceptive activity and mechanism of ß-carboline alkaloids 1-4 which were extracted from the roots of P. tunicoides. MATERIALS AND METHODS: The analgesic effects were evaluated using peripheral and central pain mouse models of nociception, including the formalin test and the tail flick test. The levels of glutamic acid (Glu) and nitric oxide (NO) in cerebellar cortexes and spinal cords (L4-6) were determined. The anti-inflammatory of all compounds were then assessed on RAW264.7 cells. RESULTS: Our results showed that compounds 1-4 had significant analgesic effects on both phases of formalin test of mice. Furthermore, all compounds showed suppressive effects on Glu in the brain and NO levels in the brain cortex and the spinal cord. Except for compound 1, the others could extend the pain threshold of hot water tail-flick in mice. In addition, compounds 2 and 3 (60 µmol/kg) could decrease GABAAα1 protein levels in spinal cord. All compounds exhibited anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells with half-maximal inhibitory concentration (IC50) 1.1-34.9 µM. CONCLUSION: ß-carboline alkaloids from the roots of P. tunicoides had significant analgesic activity by both central and peripheral mechanisms. Our findings suggested that regulating the release of NO or Glu or GABAα1 are some of the mechanisms of analgesic activity of ß-carboline alkaloids.

Pseudosterins A-C, Three 1-Ethyl-3-formyl-ß-carbolines from Pseudostellaria heterophylla and Their Cardioprotective Effects.

Pseudostellaria heterophylla is used in China not only as a functional food but also as an herb to tonify the spleen, enhance immunity, and treat palpitation. Our previous investigation showed that a fraction enriched in glycosides obtained from the roots of P. heterophylla possessed pronounced protective effects on H9c2 cells against CoCl2-induced hypoxic injury. However, the active compounds responsible for the observed effects were still unknown. In the current investigation, pseudosterins A-C (1-3), three new alkaloids with a 1-ethyl-3-formyl-ß-carboline skeleton, together with polydatin, have been isolated from the active fraction. Their structures were elucidated on the basis of spectroscopic analysis and quantum chemical calculations. The four compounds showed cardioprotective effects against sodium hydrosulfite-induced hypoxia-reoxygenation injury in H9c2 cells, with the three alkaloids being more potent. This is also the first report of alkaloids with a ß-carboline skeleton isolated from P. heterophylla as cardioprotective agents.

Dehydrocrenatidine extracted from Picrasma quassioides induces the apoptosis of nasopharyngeal carcinoma cells through the JNK and ERK signaling pathways.

Nasopharyngeal carcinoma (NPC) is an indicator disease in Asia due to its unique geographical and ethnic distribution. Dehydrocrenatidine (DC) is a ß­carboline alkaloid abundantly present in Picrasma quassioides (D. Don) Benn, a deciduous shrub or small tree native to temperate regions of southern Asia, and ß­carboline alkaloids play anti­inflammatory and antiproliferative roles in various cancers. However, the mechanism and function of DC in human NPC cells remain only partially explored. The present study aimed to examine the cytotoxicity and biochemical role of DC in human NPC cells. The MTT method, cell cycle analysis, DAPI determination, Annexin V/PI double staining, and mitochondrial membrane potential examination were performed to evaluate the effects of DC treatment on human NPC cell lines. In addition, western blotting analysis was used to explore the effect of DC on apoptosis and signaling pathways in related proteins. The analysis results confirmed that DC significantly reduced the viability of NPC cell lines in a dose­ and time­dependent manner and induced apoptosis through internal and external apoptotic pathways (including cell cycle arrest, altered mitochondrial membrane potential, and activated death receptors). Western blot analysis illustrated that DC's effect on related proteins in the mitogen­activated protein kinase pathway can induce apoptosis by enhancing ERK phosphorylation and inhibiting Janus kinase (JNK) phosphorylation. Notably, DC induced apoptosis by affecting the phosphorylation of JNK and ERK, and DC and inhibitors (SP600125 and U0126) in combination restored the overexpression of p­JNK and p­ERK. To date, this is the first study to confirm the apoptosis pathway induced by DC phosphorylation of p­JNK and p­REK in human NPC. On the basis of evidence obtained from this study, DC targeting the inhibition of NPC cell lines may be a promising future strategy for NPC treatment.

Cytotoxicity of fagaramide derivative and canthin-6-one from Zanthoxylum (Rutaceae) species against multidrug resistant leukemia cells.

In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 µM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia cells. Compounds 3 and 6 showed good selectivity on leukemia cells than normal cells. In future studies 3 should be tested against a panel of drug resistant human cells.

FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer.

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.

Pegaharmols A-B, Axially Chiral ß-Carboline-quinazoline Dimers from the Roots of Peganum harmala.

Two nonbiaryl axially chiral ß-carboline-quinazoline dimers, pegaharmols A (1) and B (2), were isolated from the roots of Peganum harmala. Their planar structures were elucidated by the spectroscopic methods of high-resolution mass spectrometry and 1D and 2D nuclear magnetic resonance (NMR). The stereochemistry was established by a comparison between the experimental data of NMR and electronic circular dichroism and the computed data by quantum mechanical calculations. It is discovered for the first time that the ß-carboline at the C-8 position is bonded to the vasicine at the C-9 position. 1 exhibited moderate cytotoxic activity against HL-60 and A549 cell lines.

ß-Carbolines in Experiments on Laboratory Animals.

Some studies have ascribed a protective effect against neurodegenerative diseases to the ß-carbolines harman (H) and norharman (NH), which occur mostly in coffee and coffee substitutes. We determined the concentrations of ß-carbolines and undesirable compounds (such as acrylamide) in roasted coffee substitute ingredients and found that chicory coffee was optimal. Two in vivo experiments were conducted with seventeen-month-old male Sprague Dawley rats fed a diet with the addition of pure carboline standards in the first stage, and chicory in the second. We observed an increase in the level of H and NH in blood plasma, as well as higher activity of animals in the battery behavioral test, particularly in the second stage. The results of in vitro studies-particularly the level of the expression in brain tissue of genes associated with aging processes and neurodegenerative diseases-clearly show the benefits of a diet rich in ß-carbolines.

Pao Pereira Extract Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by inhibiting 5α-Reductase.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in the urinary system of elderly men. Pao extract is an herbal preparation of the bark of the Amazon rainforest tree Pao Pereira (Geissospermum vellosii), which was reported to inhibit prostate cancer cell proliferation. Herein we investigated the therapeutic potential of Pao extract against BPH development in a testosterone-induced BPH rat model. The administration of testosterone induced the prostate enlargement, compared with the sham operated group with vehicle treatment. The BPH/Pao group showed reduced prostate weight comparable with BPH/finasteride group. Notably, Pao treatment did not significantly reduce body weights and sperm number of rats, compared with the control group. Furthermore, Pao extract treatment reduced the proliferative index in prostate glands and testosterone-induced expression levels of AR, as well as androgen-associated proteins such as SRD5A1 and PSA. Moreover, Pao extract and its active component, flavopereirine, induced cytotoxicity on human prostate epithelial RWPE-1 cells in a dose- and time- dependent manner with G2/M arrest. Consistently, Pao extract and flavopereirine suppressed the expression levels of SRD5A1, AR and PSA, respectively. Together, these data demonstrated that Pao extract suppresses testosterone-induced BPH development through inhibiting AR activity and expression, and suggested that Pao extract may be a promising and relative safe agent for BPH.

1-Carbomethoxy-ß-Carboline, Derived from Portulaca oleracea L., Ameliorates LPS-Mediated Inflammatory Response Associated with MAPK Signaling and Nuclear Translocation of NF-κB.

Portulaca oleracea is as a medicinal plant known for its neuroprotective, hepatoprotective, antidiabetic, antioxidant, anticancer, antimicrobial, antiulcerogenic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of P. oleracea extract (95% EtOH) remain unknown. Here, we hypothesized that alkaloids, the most abundant constituents in P. oleracea extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-22) using nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) and screened their effects on NO production in lipopolysaccharide (LPS)-induced macrophages. Compound 20, 1-carbomethoxy-ß-carboline, as an alkaloid structure, ameliorated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and proinflammatory cytokines associated with the mitogen-activated protein kinase (MAPK) pathways, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Subsequently, we observed that compound 20 suppressed nuclear translocation of nuclear factor κB (NF-κB) using immunocytochemistry. Moreover, we recently reported that compound 8, trans-N-feruloyl-3', 7'-dimethoxytyramine, was originally purified from P. oleracea extracts. Our results suggest that 1-carbomethoxy-ß-carboline, the most effective anti-inflammatory agent among alkaloids in the 95% EtOH extract of P. oleracea, was suppressing the MAPK pathway and nuclear translocation of NF-κB. Therefore, P. oleracea extracts and specifically 1-carbomethoxy-ß-carboline may be novel therapeutic candidates for the treatment of inflammatory diseases associated with the activation of MAPKs and NF-κB.

A new cinnamamide derivative and two new ß-carboline alkaloids from the stems of Picrasma quassioides.

Picrasamide A (1), a new cinnamamide derivative, together with two new ß-carboline alkaloids (2 and 3) and five known ß-carboline alkaloids (4-8) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated by detailed analyses of UV, IR, HRESIMS, and NMR data. Compound 1 was the first case of cinnamamide derivative from genus Picrasma. The AChE inhibitory activity and the antimicrobial activity of 1-8 were assessed. In addition, preliminary structure-activity relationships of these ß-carboline alkaloids on the AChE inhibitory activity and antimicrobial activity were proposed.

ß-carboline alkaloids attenuate bleomycin induced pulmonary fibrosis in mice through inhibiting NF-kb/p65 phosphorylation and epithelial-mesenchymal transition.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Arenaria kansuensis is used in traditional medicine to treat lung inflammation for a long time. However, the anti-pulmonary fibrosis effect and its corresponding bioactive constituents of this plant have not been studied extensively. AIM OF THE STUDY: The purpose of this study was to investigate the anti-pulmonary fibrosis effect and its corresponding bioactive constituents of A. kansuensis and its possible mechanism. MATERIALS AND METHODS: In vivo experiment, the anti-pulmonary fibrosis effects of the fraction (Part1) enriched from ethyl acetate extracts of the whole plant A. kansuensis were evaluated through bleomycin (BLM)-induced pulmonary fibrosis mice (five groups, n = 10) daily at doses of 50, 100 and 150 mg/kg for 15 days. In vitro experiment, the anti-inflammation and reversed epithelial-mesenchymal transition (EMT) effect of 12 ß-carboline alkaloids isolated from Part1 were evaluated through lipopolysaccharide (LPS)-induced RAW264.7 inflammatory cell model and TGF-ß1 induced A549 cell model. RESULTS: In this study, a fraction named Part1 extracted from Arenaria kansuensis presented strong anti-pulmonary fibrosis effect at the dose of 150 mg/kg. Vivo experiments showed that the survival rate and body weight of mice significantly increased after Part1 treatment. Part1 could significantly inhibit the initial of inflammation, deposition of collagen and expression of TGF-ß1 and α-SMA, moreover, the expression of E-cadherin was significantly elevated after administration of Part1. All the cure effects of Part1 were in dose dependent manner. A total of 12 ß-carboline alkaloids were identified in Part1 and they all showed suppressive effect on inflammatory cytokines including MCP-1, TNF-α, IL-6 and IL-1ß through inhibition of NF-kb/p65 phosphorylation, and that epithelial-mesenchymal transition (EMT) process was reversed by different compounds in different levels. The expression of indicators of EMT including α-SMA, vimentin and E-cadherin was significantly improved after given different ß-carboline alkaloids. CONCLUSIONS: This study showed that antifibrogenic effect of ß-carboline alkaloids was due to inhibiting the initial of inflammation through NF-kb/p65 pathway and reversing the process of EMT.