Ginsenoside Rh4 alleviates gastrointestinal mucositis and enhances chemotherapy efficacy through modulating gut microbiota.

BACKGROUND: Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11. PURPOSE: In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy. STUDY DESIGN: A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11. METHODS: In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA). RESULTS: The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila, which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-κB signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect. CONCLUSION: In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.

Synergistic anticancer effects of ginsenoside CK and gefitinib against gefitinib-resistant NSCLC by regulating the balance of angiogenic factors through HIF-1α/VEGF.

Drug resistance is a serious problem for gefitinib in the treatment of lung cancer. Ginsenoside CK, a metabolite of diol ginsenosides, have many excellent pharmacological activities, but whether ginsenoside CK can overcome gefitinib resistance remains unclear. In our study, the sensitizing activity of ginsenoside CK on gefitinib-resistant non-small cell lung cancer (NSCLC) in vitro and in vivo was investigated. Ginsenoside CK was confirmed to enhance the anti-proliferation, pro-apoptotic and anti-migration effects of gefitinib in primary and acquired resistant NSCLC. Furthermore, the combined administration of CK and gefitinib effectively promoted the sensitivity of lung cancer xenograft to gefitinib in vivo, and the tumor inhibition rate reached 70.97% (vs. gefitinib monotherapy 32.65%). Subsequently, tubule formation experiment and western blot results showed that co-treatment of ginsenoside CK inhibited the angiogenesis ability of HUVEC cells, and inhibited the expression of HIF-1α, VEGF, FGF and MMP2/9. More interestingly, ginsenoside CK co-treatment enhanced the expression of anti-angiogenic factor PF4, increased pericellular envelope, and promoted the normalization of vascular structure. In conclusion, ginsenoside CK improved the resistance of gefitinib by regulating the balance of angiogenic factors through down-regulating the HIF-1α/VEGF signaling pathway, providing a theoretical basis for improving the clinical efficacy of gefitinib and applying combined strategies to overcome drug resistance.

Expression, characterization and antivascular activity of amino acid sequence repeating collagen hexadecapeptide.

Type V collagen is an essential component of the extracellular matrix (ECM), and its remodeling releases specific protein fragments that can specifically inhibit endothelial cell responses such as proliferation, migration, and invasion. In this study, we have successfully constructed two engineered strains of Pichia pastoris capable of producing recombinant collagen through a new genetic engineering approach. Through high-density fermentation, the expression of 1605 protein and 1610 protein could reach 2.72 g/L and 4.36 g/L. With the increase of repetition times, the yield also increased. Bioactivity analysis showed that recombinant collagen could block the angiogenic effect of FGF-2 on endothelial cells by eliminating FGF-2-induced endothelial cell migration and invasion. Collectively, the recombinant proteins we successfully expressed have a wide range of potential for inhibiting angiogenesis in the biomaterials and biomedical fields.

Ginsenoside Rk1 induces autophagy-dependent apoptosis in hepatocellular carcinoma by AMPK/mTOR signaling pathway.

Hepatocellular carcinoma (HCC) is the third most lethal cancer in the world. Recent studies have shown that suppression of autophagy plays an important role in the development of HCC. Ginsenoside Rk1 is a protopanaxadiol saponin isolated from ginseng and has a significant anti-tumor effect, but its role and mechanism in HCC are still unclear. In this study, a mouse liver cancer model induced by diethylnitrosamine and carbon tetrachloride (DEN + CCl4) was employed to investigate the inhibitory effect of Rk1 on HCC. The results demonstrate that ginsenoside Rk1 effectively inhibits liver injury, liver fibrosis, and cirrhosis during HCC progression. Transcriptome data analysis of mouse liver tissue reveals that ginsenoside Rk1 significantly regulates the AMPK/mTOR signaling pathway, autophagy pathway, and apoptosis pathway. Subsequent studies show that ginsenoside Rk1 induces AMPK protein activation, upregulates the expression of autophagy marker LC3-II protein to promote autophagy, and then downregulates the expression of Bcl2 protein to trigger a caspase cascade reaction, activating AMPK/mTOR-induced toxic autophagy to promote cells death. Importantly, co-treatment of ginsenoside Rk1 with autophagy inhibitors can inhibit apoptosis of HCC cells, once again demonstrating the ability of ginsenoside Rk1 to promote autophagy-dependent apoptosis. In conclusion, our study demonstrates that ginsenoside Rk1 inhibits the development of primary HCC by activating toxic autophagy to promote apoptosis through the AMPK/mTOR pathway. These findings confirm that ginsenoside Rk1 is a promising new strategy for the treatment of HCC.

Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis.

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3 (Rk3) on CRC and gut microbiota remains unclear. Therefore, the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation. Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors, repairs intestinal barrier damage, and regulates the gut microbiota imbalance caused by CRC, including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis, and clearance of pathogenic Desulfovibrio. Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids, particularly by upregulating glutamine, which has the potential to regulate the immune response. Furthermore, we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) signaling pathways, which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. These results indicate that Rk3 modulates gut microbiota, regulates ILC3s immune response, and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors. More importantly, the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota. In summary, these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

Ginsenoside Rg5 inhibits lipid accumulation and hepatocyte apoptosis via the Notch1 signaling pathway in NASH mice.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease that lacks an FDA-approved treatment medicine. Despite the known antitumor and hypoglycemic properties of Ginsenoside Rg5, its effects and underlying mechanisms in the context of NASH remain largely unexplored. PURPOSE: This study aims to investigate the effect of Rg5 on NASH mice induced by a high-fat diet and CCl4. STUDY DESIGN: In vivo experiments, a mouse NASH model was established by a HFHC diet plus intraperitoneal injection of low-dose CCl4. In vitro experiments, a cellular steatosis model was established using free fatty acids (FFA) induced HepG2 cells. In addition, a fibrogenesis model was established using HSC-LX2 cells. METHODS: The effects of Ginsenoside Rg5 on lipid accumulation and oxidative damage were analyzed by ELISA kit, H&E staining, Oil Red O staining, flow cytometry and Western blot. The effects of Ginsenoside Rg5 on liver fibrosis were analyzed by Masson staining, Sirus Red staining, immunohistochemistry and Western blot. The effect of Ginsenoside Rg5 on Notch1 signaling pathway in liver was studied by protein Oil Red staining, protein immunoblotting and immunofluorescence. RESULTS: In terms of lipid accumulation, Rg5 has the ability to regulate key proteins related to lipogenesis, thereby inhibiting hepatic lipid accumulation and oxidative stress. Additionally, Rg5 can reduce the occurrence of hepatocyte apoptosis by regulating the p53 protein. Moreover, after Rg5 intervention, the presence of fibrotic proteins (α-SMA, Collagen 1, TGF-ß) in the liver is significantly suppressed, thus inhibiting liver fibrosis. Lastly, Rg5 leads to a decrease in the expression levels of Notch1 and its ligand Jagged-1 in the liver. CONCLUSION: In summary, the regulatory effects of Rg5 on the Notch1 signaling pathway play a crucial role in modulating hepatic lipid metabolism and preventing hepatocyte apoptosis, thereby impeding the progression of NASH. These findings highlight the potential of Rg5 as a promising natural product for interventions targeting NASH.

Rapid dissolution microneedle based on polyvinyl alcohol/chitosan for local oral anesthesia.

At present, the main clinical methods of oral local anesthesia are direct injection of anesthetic and surface ointment. However, the pain and fear caused by the injection, the discomfort of topical anesthetic creams, and the scour and moist oral environment during the procedure pose great challenges to oral anesthesia. Herein, we designed a Lido-PVP/PVA DMNP microneedle (MN) for oral local anesthesia. The microneedle tip was consisted of Polyvinylpyrrolidone/Polyvinyl alcohol (PVP/PVA), which can quickly dissolve and release the lidocaine hydrochloride (Lido) drug within 5 min to achieve rapid anesthesia. The backing was composed of polyvinyl alcohol/chitosan (PVA/CS), and its excellent adhesion can overcome saliva erosion and anchor firmly to the oral mucosa, significantly improving the utilization rate of drugs, as well as the patient compliance. MNs have good mechanical properties for tissue insertion while possessing high drug loading (3 mg/MNs). Von Frey tests proved that MNs showed a faster and more effective local anesthetic effect (anesthesia takes effect at 5 min) compared to cream (anesthesia takes effect at 30 min). In addition, the excellent biocompatibility and no skin irritation endowed Lido-PVP/PVA DMNP MNs a great potential for oral local anesthesia in the oral cavity.

Molecularly imprinted solid-phase extraction combined with non-ionic hydrophobic deep eutectic solvents dispersed liquid-liquid microextraction for efficient enrichment and determination of the estrogens in serum samples.

Hormonal drugs in biological samples are usually in low concentration and highly intrusive. It is of great significance to enhance the sensitivity and specificity of the detection process of hormone drugs in biological samples by utilizing appropriate sample pretreatment methods for the detection of hormone drugs. In this study, a sample pretreatment method was developed to effectively enrich estrogens in serum samples by combining molecularly imprinted solid-phase extraction, which has high specificity, and non-ionic hydrophobic deep eutectic solvent-dispersive liquid-liquid microextraction, which has a high enrichment ability. The theoretical basis for the effective enrichment of estrogens by non-ionic hydrophobic deep eutectic solvent was also computed by simulation. The results showed that the combination of molecularly imprinted solid-phase extraction and deep eutectic solvent-dispersive liquid-liquid microextraction could improve the sensitivity of HPLC by 33∼125 folds, and at the same time effectively reduce the interference. In addition, the non-ionic hydrophobic deep eutectic solvent has a relatively low solvation energy for estrogen and possesses a surface charge similar to that of estrogen, and thus can effectively enrich estrogen. The study provides ideas and methods for the extraction and determination of low-concentration drugs in biological samples and also provides a theoretical basis for the application of non-ionic hydrophobic deep eutectic solvent extraction.

Selumetinib overcomes gefitinib primary and acquired resistance by regulating MIG6/STAT3 in NSCLC.

Gefitinib, as the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has achieved great advances in the treatment of non-small cell lung cancer (NSCLC), but drug resistance will inevitably occur. Therefore, exploring the resistance mechanism of gefitinib and developing new combination treatment strategies are of great importance. In our study, the results showed that selumetinib (AZD6244) synergistically inhibited the proliferation of NSCLC with gefitinib. Selumetinib also enhanced gefitinib-induced apoptosis and migration inhibition ability in gefitinib-resistant lung cancer cell lines. Subsequently, the negative regulation between MIG6 and STAT3 was observed and verified through the STRING database and western blotting assays. Sustained activation of STAT3 was significantly downregulated when co-treatment with selumetinib in gefitinib-resistant cells. However, the downregulation of p-STAT3, resulting from the combination of selumetinib and gefitinib was counteracted by the deletion of MIG6, suggesting that selumetinib enhanced gefitinib sensitivity by regulating MIG6/STAT3 in NSCLC. In contrast, p-STAT3 was further inhibited after treatment with gefitinib and selumetinib when MIG6 was overexpressed. Furthermore, the combined administration of selumetinib and gefitinib effectively promoted the sensitivity of lung cancer xenografts to gefitinib in vivo, and the tumor inhibition rate reached 81.49%, while the tumor inhibition rate of the gefitinib monotherapy group was only 31.95%. Overall, MIG6/STAT3 negative regulation plays an important role in the sustained activation of STAT3 and the resistance to EGFR-TKIs. Our study also suggests that EGFR-TKIs combined with MEK1/2 inhibitors, such as selumetinib, may be beneficial to those NSCLC patients who develop a primary or acquired resistance to EGFR-TKIs, providing theoretical support for combining TKIs and selumetinib in clinical cancer treatment.

Ginsenosides: a potential natural medicine to protect the lungs from lung cancer and inflammatory lung disease.

Lung cancer is the malignancy with the highest morbidity and mortality. Additionally, pulmonary inflammatory diseases, such as pneumonia, acute lung injury, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF), also have high mortality rates and can promote the development and progression of lung cancer. Unfortunately, available treatments for them are limited, so it is critical to search for effective drugs and treatment strategies to protect the lungs. Ginsenosides, the main active components of ginseng, have been shown to have anti-cancer and anti-inflammatory activities. In this paper, we focus on the beneficial effects of ginsenosides on lung diseases and their molecular mechanisms. Firstly, the molecular mechanism of ginsenosides against lung cancer was summarized in detail, mainly from the points of view of proliferation, apoptosis, autophagy, angiogenesis, metastasis, drug resistance and immunity. In in vivo and in vitro lung cancer models, ginsenosides Rg3, Rh2 and CK were reported to have strong anti-lung cancer effects. Then, in the models of pneumonia and acute lung injury, the protective effect of Rb1 was particularly remarkable, followed by Rg3 and Rg1, and its molecular mechanism was mainly associated with targeting NF-κB, Nrf2, MAPK and PI3K/Akt pathways to alleviate inflammation, oxidative stress and apoptosis. Additionally, ginsenosides may also have a potential health-promoting effect in the improvement of COPD, asthma and PF. Furthermore, to overcome the low bioavailability of CK and Rh2, the development of nanoparticles, micelles, liposomes and other nanomedicine delivery systems can significantly improve the efficacy of targeted lung cancer treatment. To conclude, ginsenosides can be used as both anti-lung cancer and lung protective agents or adjuvants and have great potential for future clinical applications.

The Progress in the Application of Dissolving Microneedles in Biomedicine.

In recent years, microneedle technology has been widely used for the transdermal delivery of substances, showing improvements in drug delivery effects with the advantages of minimally invasive, painless, and convenient operation. With the development of nano- and electrochemical technology, different types of microneedles are increasingly being used in other biomedical fields. Recent research progress shows that dissolving microneedles have achieved remarkable results in the fields of dermatological treatment, disease diagnosis and monitoring, and vaccine delivery, and they have a wide range of application prospects in various biomedical fields, showing their great potential as a form of clinical treatment. This review mainly focuses on dissolving microneedles, summarizing the latest research progress in various biomedical fields, providing inspiration for the subsequent intelligent and commercial development of dissolving microneedles, and providing better solutions for clinical treatment.

Lung cancer treatment potential and limits associated with the STAT family of transcription factors.

Lung cancer is one of the mortal cancers and the leading cause of cancer-related mortality, with a cancer survival rate of fewer than 5% in developing nations. This low survival rate can be linked to things like late-stage detection, quick postoperative recurrences in patients receiving therapy, and chemoresistance developing against various lung cancer treatments. Signal transducer and activator of transcription (STAT) family of transcription factors are involved in lung cancer cell proliferation, metastasis, immunological control, and treatment resistance. By interacting with specific DNA sequences, STAT proteins trigger the production of particular genes, which in turn result in adaptive and incredibly specific biological responses. In the human genome, seven STAT proteins have been discovered (STAT1 to STAT6, including STAT5a and STAT5b). Many external signaling proteins can activate unphosphorylated STATs (uSTATs), which are found inactively in the cytoplasm. When STAT proteins are activated, they can increase the transcription of several target genes, which leads to unchecked cellular proliferation, anti-apoptotic reactions, and angiogenesis. The effects of STAT transcription factors on lung cancer are variable; some are either pro- or anti-tumorigenic, while others maintain dual, context-dependent activities. Here, we give a succinct summary of the various functions that each member of the STAT family plays in lung cancer and go into more detail about the advantages and disadvantages of pharmacologically targeting STAT proteins and their upstream activators in the context of lung cancer treatment.

Ginsenoside Rh4 Improves Hepatic Lipid Metabolism and Inflammation in a Model of NAFLD by Targeting the Gut Liver Axis and Modulating the FXR Signaling Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a series of disorders of liver metabolism caused by the accumulation of lipids in the liver, which is considered the main cause of hepatocellular carcinoma. Our previous study demonstrated the promising efficacy of ginsenoside Rh4 in improving the intestinal tract and its related metabolites. Meanwhile, many studies in the literature have investigated the gut microbiota and its metabolites, such as bile acids (BAs) and short-chain fatty acids (SCFAs), which play a key role in the pathogenesis of NAFLD. Therefore, this study focused on whether Rh4 could achieve therapeutic effects on NAFLD through the gut-liver axis. The results showed that Rh4 exhibited sound therapeutic effects on the NAFLD model induced by the Western diet and CCl4 in mice. In the liver, the degrees of hepatic steatosis, lobular inflammation levels, and bile acid in the liver tissue were improved after Rh4 treatment. At the same time, Rh4 treatment significantly increased the levels of intestinal SCFAs and BAs, and these changes were accompanied by the complementary diversity and composition of intestinal flora. In addition, correlation analysis showed that Rh4 affected the expression of proteins involved in the farnesoid X receptor (FXR) signaling pathway in the liver and intestine, which modulates hepatic lipid metabolism, inflammation, and proteins related to bile acid regulation. In conclusion, our study provides a valuable insight into how Rh4 targets the gut-liver axis for the development of NAFLD, which indicates that Rh4 may be a promising candidate for the clinical therapy of NAFLD.

Metabolomic and transcriptomic analysis of cold plasma promoting biosynthesis of active substances in broccoli sprouts.

INTRODUCTION: Broccoli sprouts have great health and commercial value because they are rich in sulforaphane, a special bioactive compound that helps to prevent chronic diseases, such as cancer and cardiovascular disease. OBJECTIVE: The aim of this study was to increase the levels of active substances in broccoli sprouts and understand their metabolic mechanisms. METHODOLOGY: Metabolomics based on liquid chromatography-tandem mass spectrometry and transcriptome analysis were combined to analyse the enrichment of metabolites in broccoli sprouts treated with cold plasma. RESULTS: After 2 min of cold plasma treatment, the contents of sulforaphane, glucosinolates, total phenols, and flavonoids, as well as myrosinase activity, were greatly improved. Transcriptomics revealed 7460 differentially expressed genes in the untreated and treated sprouts. Metabolomics detected 6739 differential metabolites, including most amino acids, their derivatives, and organic acids. Enrichment analyses of metabolomics and transcriptomics identified the 20 most significantly differentially expressed metabolic pathways. CONCLUSIONS: Overall, cold plasma treatment can induce changes in the expression and regulation of certain metabolites and genes encoding active substances in broccoli sprouts.

Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Ginsenoside Rk3, an important and rare saponin in heat-treated ginseng, is generated from Rg1 and has a smaller molecular weight. However, the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized. Here, we investigated the mechanism by which ginsenoside Rk3, a tetracyclic triterpenoid rare ginsenoside, inhibits the growth of HCC. We first explored the possible potential targets of Rk3 through network pharmacology. Both in vitro (HepG2 and HCC-LM3 cells) and in vivo (primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice) studies revealed that Rk3 significantly inhibits the proliferation of HCC. Meanwhile, Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC. Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway to inhibit HCC growth, which was validated by molecular docking and surface plasmon resonance. In conclusion, we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC. Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.

Structure-activity relationship, bioactivities, molecular mechanisms, and clinical application of nuciferine on inflammation-related diseases.

Nuciferine aporphine alkaloid mainly exists in Nelumbo nucifera Gaertn and is a beneficial to human health, such as anti-obesity, lowering blood lipid, prevention of diabetes and cancer, closely associated with inflammation. Importantly, nuciferine may contribute to its bioactivities by exerting intense anti-inflammatory activities in multiple models. However, no review has summarized the anti-inflammatory effect of nuciferine. This review critically summarized the information regarding the structure-activity relationships of dietary nuciferine. Moreover, biological activities and clinical application on inflammation-related diseases, such as obesity, diabetes, liver, cardiovascular diseases, and cancer, as well as their potential mechanisms, involving oxidative stress, metabolic signaling, and gut microbiota has been reviewed. The current work provides a better understanding of the anti-inflammation properties of nuciferine against multiple diseases, thereby improving the utilization and application of nuciferine-containing plants across functional food and medicine.

Ginsenoside Rk3 Regulates Nonalcoholic Steatohepatitis by Modulation of Intestinal Flora and the PI3K/AKT Signaling Pathway in C57BL/6 Mice.

Non-alcoholic steatohepatitis (NASH) has become the most important reason of liver disease around the world and is predisposed to further progression to cirrhosis and hepatocellular carcinoma. Ginsenoside Rk3 has been reported to have a plenty of biological activities, including anti-apoptotic, anti-anemia, and protective effects against acute kidney injury. However, whether ginsenoside Rk3 can improve NASH has not been reported yet. Therefore, the purpose of this study is to investigate the protective effect of ginsenoside Rk3 against NASH and its mechanism of action. C57BL/6 mice were treated with different dosages of ginsenoside Rk3 after being established as a NASH model. Our results showed that Rk3 administration significantly improved liver inflammation, lipid deposition, and fibrosis caused by a high-fat-high-cholesterol (HFHC) diet and CCl4 injection in mice. Notably, ginsenoside Rk3 was discovered significantly to inhibit the PI3K/AKT signaling pathway. Additionally, treatment with ginsenoside Rk3 remarkably amended the abundance of short-chain fatty acids. These changes were associated with beneficial variations to the variety and composition of the intestinal microbiota. In conclusion, ginsenoside Rk3 ameliorates hepatic non-alcoholic lipid inflammation and triggers changes in the beneficial intestinal flora, helping to reveal host-microbe interactions. The outcomes of this study indicate that ginsenoside Rk3 is a promising drug candidate for the treatment of NASH.

Regulation of inflammation in cancer by dietary eicosanoids.

BACKGROUND: Cancer is a major burden of disease worldwide and increasing evidence shows that inflammation contributes to cancer development and progression. Eicosanoids are derived from dietary polyunsaturated fatty acids, such as arachidonic acid (AA), and are mainly produced by a series of enzymatic pathways that include cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 epoxygenase (CYP). Eicosanoids consist of at least several hundred individual molecules and play important roles in the inflammatory response and inflammation-related cancers. SCOPE AND APPROACH: Dietary sources of AA and biosynthesis of eicosanoids from AA through different metabolic pathways are summarized. The bioactivities of eicosanoids and their potential molecular mechanisms on inflammation and cancer are revealed. Additionally, current challenges and limitations in eicosanoid research on inflammation-related cancer are discussed. KEY FINDINGS AND CONCLUSIONS: Dietary AA generates a large variety of eicosanoids, including prostaglandins, thromboxane A2, leukotrienes, cysteinyl leukotrienes, lipoxins, hydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Eicosanoids exert different bioactivities and mechanisms involved in the inflammation and related cancer developments. A deeper understanding of eicosanoid biology may be advantageous in cancer treatment and help to define cellular targets for further therapeutic development.

Gastroprotective effects of ginsenoside Rh4 against ethanol-induced gastric mucosal injury by inhibiting the MAPK/NF-κB signaling pathway.

Ginsenoside Rh4, a bioactive component extracted from Panax ginseng, exhibits various pharmacological activities, such as anti-inflammatory, anti-oxidation, anti-diabetes, anti-obesity, antitumor and immunity enhancement. However, the gastroprotective effect of ginsenoside Rh4 remains unknown. The present study evaluated the gastroprotective effect and potential mechanism of ginsenoside Rh4 in an ethanol-induced gastric ulcer model. Ginsenoside Rh4 (15, 30, and 60 mg kg-1) and omeprazole (30 mg kg-1) were administered orally for 7 days. The results showed that pretreatment with ginsenoside Rh4 reduced the gastric injury area and percentage of mucosal lesions in gastric tissue. Besides, treatment with ginsenoside Rh4 increased superoxide dismutase (SOD) activity, glutathione (GSH) and nitric oxide (NO) levels, reduced the content of malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), mediated the prostaglandin E-2-cyclooxygenase-2 (PGE2-Cox-2) pathway, and mitigated inflammation and oxidative stress via blockade of proinflammatory mitogen-activated protein kinase-nuclear factor κB (MAPK/NF-κB) signaling pathways. Furthermore, ginsenoside Rh4 significantly enhanced the protein expression of B-cell lymphoma gene 2 (Bcl-2), decreased the protein expression of Bcl-2-associated X protein (Bax) and tumor necrosis factor receptor superfamily member 6 (Fas), and inhibited the number of apoptotic cells in gastric tissues. The present work demonstrated that ginsenoside Rh4 exerted a considerable gastroprotective effect against ethanol-induced gastric ulcers in rats.

NIR- and pH-responsive injectable nanocomposite alginate-graft-dopamine hydrogel for melanoma suppression and wound repair.

Surgical excision, chemotherapy, and radiotherapy are the main approaches used for treating melanoma. Unfortunately, surgical excision usually inevitably causes large area skin defects. In addition, chemotherapy and radiotherapy are often accompanied by adverse reactions and multi-drug resistance. To overcome these limitations, a near-infrared (NIR)- and pH-responsive injectable nanocomposite hydrogel was developed using sodium alginate-graft-dopamine (SD) and biomimetic polydopamine-Fe(III)-doxorubicin nanoparticles (PFD NPs) for treating melanoma and promoting skin regeneration. Firstly, the SD/PFD hydrogel can precisely deliver anti-cancer agents to the tumor site to reduce its loss and off-target toxicity. Then, PFD can convert light into heat energy under NIR irradiation to kill cancer cells. Meanwhile, doxorubicin can be administered continuously and controllably by NIR- and pH-responsive. Additionally, the SD/PFD hydrogel can also relieve tumor hypoxia by decomposing endogenous hydrogen peroxide (H2O2) into oxygen (O2). Therefore, photothermal, chemotherapy, and nanozyme synergetic therapy resulted in the tumor suppression. Specifically, the SA-based hydrogel can kill bacteria, scavenge reactive oxygen species, promote the proliferation and migration of cells, and significantly accelerate skin regeneration. Therefore, this study provides a safe and effective strategy for melanoma treatment and wound repair.