Bibliometric and visual analysis in the field of traditional Chinese medicine in cancer from 2002 to 2022.

Objective: Traditional Chinese medicine (TCM) has been used as a complementary treatment for cancer patients, but there has been no quantitative comprehensive analysis of TCM's efficacy. The purpose of this paper is to explore the current status and hotspots of TCM in cancer research from 2002 to 2022 and to provide a reference for future research. Methods: We retrieved articles published between 2002 and 2022 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace software. Results: A total of 7,129 articles were included in this study. The publication rate of TCM cancer research increased steadily from 2002 to 2022, with a rapid increase from 2010 to 2021. China was the country with the most published articles, followed by the United States, Republic of Korea, Germany, and Japan. China was also the country with the most international collaborations, and China Medical University and Shanghai University of Traditional Chinese Medicine were the most representative cooperation centers. The Journal of Ethnopharmacology was the most published and cited journal. Apoptosis, expression, in vitro, activation, and other related keywords were commonly used in these articles. Breast cancer, colorectal cancer, gastric cancer, liver cancer, and lung cancer were the most studied cancer types in TCM research. Pathway-related apoptosis, anti-inflammation, and oxidative stress were the hotspots and trends of TCM's anti-cancer mechanism. Metabolomics combined with network pharmacology was the main research method. Conclusion: Traditional Chinese medicine as an anti-cancer drug has received increasing attention from researchers worldwide, and it is expected to be a hotspot for developing new anti-cancer drugs in the future. Our study provides a comprehensive analysis of the current status and hotspots of TCM cancer research, which could serve as a valuable reference for future studies.

Hepatoprotective effect of total flavonoids of Mallotus apelta (Lour.) Muell.Arg. leaf against carbon tetrachloride-induced liver fibrosis in rats via modulation of TGF-ß1/Smad and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mallotus apelta (Lour.) Muell.Arg. is a well-known traditional Chinese medicine (TCM) used for anti-inflammatory, hemostasis and chronic hepatitis. AIM: The purpose of this study was to explore the antifibrotic effect of total flavonoids of Mallotus apelta leaf (TFM) and its potential mechanism. METHODS: Hepatic fibrosis was induced by carbon tetrachloride (CCl4) in rats. The CCl4-induced rats received intragastric administration of colchicine (0.2 mg/kg per day), TFM (25, 50, 100 mg/kg per day) and the equal vehicle was given to normal rats. Pathological evaluation in hepatic tissue were examined by hematoxylin and eosin (HE) staining. And the levels of serum biochemical parameters were detected by automatic biochemical analysis. Meanwhile, the collagen deposition in liver was observed by staining with Masson's trichrome. Collagenic parameters and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA) kits. Additionally, corresponding assay kit was used to estimate the antioxidant enzyme and lipid peroxidation. In order to explore the potential mechanism of anti-fibrotic effects in TFM, the expressions of liver fibrosis related gene and protein were analyzed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot. RESULTS: The CCl4-induced hepatic fibrosis were inhibited dose-dependently in rats by TFM. The results showed that the key hallmarks of liver injury including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB) and total protein (TP) in the serum were reversed in CCl4-induced hepatic fibrosis rats which were treated by TFM. Furthermore, TFM significantly alleviates collagen accumulation and reduces the contents of hydroxyproline (Hyp), Type III precollagen (PC-III), collagen I (Col I), hyaluronic acid (HA) and laminin (LN). RT-PCR and Western blot results showed that TFM markedly inhibits liver fibrosis hallmark factor α-smooth muscle actin (α-SMA) expressions in CCl4-induced hepatic fibrosis rats. Moreover, TFM alleviated the oxidative stress and lipid peroxidation in rats induced by CCl4. TFM also attenuated the pro-inflammatory cytokines including interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) via inhibiting nuclear factor-κB (NF-κB) activation. Meanwhile, transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway was inhibited by TFM treatment. CONCLUSIONS: TFM can alleviate CCl4-induced hepatic fibrosis in rats, which potential mechanism may be due to its ability of reducing ECM accumulation, improving antioxidant and regulating TGF-ß1/Smad signaling pathways and NF-κB-dependent inflammatory response.

Helenalin from Centipeda minima ameliorates acute hepatic injury by protecting mitochondria function, activating Nrf2 pathway and inhibiting NF-κB activation.

Acute liver injury is a life-threatening syndrome that often caused by hepatocyte damage and is characterized by inflammatory and oxidative responses. Helenalin isolated from Centipeda minima (HCM) has been found to have anti-inflammatory and anti-oxidative effects. Here, this study aimed to investigate the effects and underlying mechanisms of HCM on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN)-induced acute liver injury. Mice were intragastrically administered with various dose of HCM for 10 days; 2 h after the final treatment, the mice were injected with 50 µg/kg LPS and 800 mg/kg D-GalN. The histopathological changes, hepatocyte apoptosis, serum cytokines, oxidative stress and inflammatory cytokines were assessed. The results showed that HCM significantly ameliorated the hepatic injury, as evidenced by the attenuation of histopathological changes and the decrease in serum aminotransferase and total bilirubin activities. HCM markedly decreased hepatocyte apoptosis by modulating the mitochondria-dependent pathway, including the increase in the Bcl-2/Bax ratio, the inhibition of caspase-3, -8 and -9, and the inhibition of cytochrome C release. Moreover, HCM strongly alleviated oxidative stress, lipid peroxidation and reactive oxygen species (ROS) generation by activating the Nrf2 signaling pathway. In addition, HCM significantly attenuated inflammatory cytokines including TNF-α, IL6 and IL-1ß as well as NO production by inhibiting TLR4 signaling transduction and NF-κB activation. In conclusion, HCM protects hepatocytes from damage induced by LPS/D-GalN, which may contribute to its ability to alleviate hepatocyte apoptosis by protecting the mitochondrial function, inhibit oxidative stress by activating the Nrf2 pathway, and attenuate inflammation by inhibiting NF-κB activation. This study demonstrates that HCM may be developed as a potential agent for the treatment of acute liver failure.

HBOA ameliorates CCl4-incuded liver fibrosis through inhibiting TGF-ß1/Smads, NF-κB and ERK signaling pathways.

An ingredient was isolated from Acanthus ilicifolius and identified as 4-hydroxy-2(3H)-benzoxazolone (HBOA). Its protective effects and underlying mechanism on liver fibrosis were investigated. Briefly, rats were intragastrically administrated with 50% CCl4 twice a week for 12 weeks to induce liver fibrosis. Meanwhile, the animals were treated with various medicines from weeks 8 to 12. Then the histological change, serum biochemical index, inflammatory factors and hepatocyte apoptosis were detected. Moreover, the TGF-ß1/Smads, NF-κB and ERK signaling pathways were also detected to illustrate the underlying mechanism. The results showed that HBOA significantly ameliorated CCl4-induced liver injury and collagen accumulation in rats, as evidenced by the histopathologic improvement. Moreover, HBOA markedly decreased hepatocyte apoptosis by regulating the expression levels of caspase-3, -9 and -12, as well as the Bcl-2 family. The mechanism study showed that HBOA significantly decreased the expressions of α-smooth muscle actin (α-SMA) and collagen and inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and its inhibitor (TIMPs). HBOA markedly alleviated oxidative stress and inflammatory cytokines through inhibiting the NF-κB pathway. In addition, HBOA significantly down-regulated the levels of TGF-ß1, Smad2/3, Smad4 and up-regulated the level of Smad7, inhibiting the TGF-ß1/Smads signaling pathway. Moreover, HBOA significantly blocked the ERK signaling pathway, leading to the inactivation of hepatic stellate cells. This study suggests that HBOA exerts a protective effect against liver fibrosis via modulating the TGF-ß1/Smads, NF-κB and ERK signaling pathways, which will be developed as a potential agent for the treatment of liver fibrosis.

Methyl helicterate inhibits hepatic stellate cell activation through downregulating the ERK1/2 signaling pathway.

The present study was to investigate the inhibitory effect of methyl helicterate (MH) on hepatic stellate cells (HSC-T6), primarily elucidating the underlying mechanism of MH against liver fibrosis. HSC-T6 cells were activated by platelet-derived growth factor (PDGF) stimulation, and then the effects of MH on cell viability, cytomembrane integrity, colony, migration, apoptosis, and cell cycle were detected. Moreover, the regulative mechanism of MH on HSCs was investigated by detecting the activation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway. The results showed that MH significantly inhibited HSC-T6 cell viability and proliferation in a concentration-dependent manner. It notably promoted the release of lactate dehydrogenase, destroying cell membrane integrity. MH also markedly inhibited HSC-T6 cell clonogenicity and migration. Moreover, MH treatment significantly induced cell apoptosis and arrested cell cycle at the G2 phase. The further study showed that MH inhibited the expression of ERK1, ERK2, c-fos, c-myc, and Ets-1, blocking the ERK1/2 pathway. In conclusion, this study demonstrates that MH significantly inhibits HSC activation and promotes cell apoptosis via downregulation of the ERK1/2 signaling pathway.

Didymin ameliorates hepatic injury through inhibition of MAPK and NF-κB pathways by up-regulating RKIP expression.

A flavone was isolated from Origanum vulgare and identified as didymin (O. vulgare didymin, OVD). The protective effect and mechanism of OVD on acute liver injury was then assessed in vivo and in vitro. Our results showed that OVD significantly alleviated CCl4-induced liver injury in mice and markedly decreased serum ALT and AST activities. OVD treatment significantly reduced CYP2E1 activity, lipid peroxidation level, ROS generation, NO production and pro-inflammatory cytokines (such as TNF-α, IL-6 and IL-1ß) in liver tissues and RAW 264.7 cells, but enhanced the hepatic antioxidative enzymes activities. Further study showed that OVD significantly inhibited the NF-κB and MAPK pathways. Interestingly, OVD notably enhanced Raf kinase inhibitor protein (RKIP) expression, and the effects of OVD on histological changes, oxidative stress and inflammation was largely abolished by the RKIP specific inhibitor locostatin. Our findings indicate that OVD can ameliorate CCl4-induced liver injury, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of MAPK and NF-κB signaling pathways.