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Abstract Current skin sensors or wound dressings fall short in addressing the complexities and challenges encountered in real‐world scenarios, lacking adequate capability to facilitate wound repair. The advancement of methodologies enabling early diagnosis, real‐time monitoring, and active regulation of drug delivery for timely comprehensive treatment holds paramount significance for complex chronic wounds. In this study, a nanocomposite hydrogel is devised for real‐time monitoring of wound condition and comprehensive treatment. Tannins and siRNA containing matrix metalloproteinase‐9 gene siRNA interference are self‐assembled to construct a degradable nanogel and modified with bovine serum albumin. The nanogel and pH indicator are encapsulated within a dual‐crosslinking hydrogel synthesized with norbornene dianhydride‐modified paramylon. The hydrogel exhibited excellent shape adaptability due to borate bonding, and the click polymerization reaction led to rapid in situ curing of the hydrogel. The system not only monitors pH, temperature, wound exudate alterations, and peristalsis during wound healing but also exhibits hemostatic, antimicrobial, anti‐inflammatory, and antioxidant properties, modulates macrophage polarization, and facilitates vascular tissue regeneration. This therapeutic approach, which integrates the monitoring of pathological parameters with comprehensive treatment, is anticipated to address the clinical issues and challenges associated with chronic diabetic wounds and infected wounds, offering broad prospects for application.

Abstract Idiopathic pulmonary fibrosis (IPF), often likened to a “tumor‐like disease,” proves more lethal than several malignancies. Although prior studies have demonstrated the lung‐protective efficacy of ginsenosides, the precise mechanism underlying their alleviative effect on IPF remains elusive. In this study, we validated the efficacy of the ginsenoside Rh4 in alleviating IPF and delved into the underlying mechanisms. Our data showed that Rh4 intervention significantly reduced mortality and hydroxyproline (HYP) content in mice. It also alleviated the pathological process of IPF by ameliorating phenomena such as alveolar wall thickening induced by IPF. In addition, in vitro cellular experiments confirmed that ginsenoside Rh4 was effective in alleviating transforming growth factor‐β1‐induced IPF model. Further analysis showed that ginsenoside Rh4 significantly reduced collagen fiber production and deposition while inhibiting the coagulation cascade signaling pathway. In addition, ginsenoside Rh4 inhibited the epithelial‐mesenchymal transition(EMT) pathway by promoting the CXCR3‐CXCL9 axis, which ultimately alleviated IPF. In conclusion, our data strongly suggest that ginsenoside Rh4 has the potential to be an innovative prophylactic drug against IPF.

Abstract Dislocation of anti‐adhesion materials, non‐specific tissue adhesion, and the induction of secondary fibrinolysis disorders are the main challenges faced by postoperative anti‐adhesion materials. Herein, a self‐leveling transient unilateral adhesive hydrogel is custom‐designed to conquer these challenges with a theoretically calculated and dual‐step tailored gellan gum (GG) as the sole agent. First, the maximum gelation temperature of GG is lowered from 42–25 °C through controlled perturbation of intra‐ and inter‐molecular hydrogen bonds, which is achieved by employing the methacrylic anhydride as a “hydrogen bond's perturbator” to form methacrylate GG (MeGG). Second, the “self‐leveling” injectability and wound shape adaptably are endowed by the formation of borate‐diol complexed MeGG (BMeGG). Finally, the transient unilateral tissue‐adhesive hydrogel (BMeGG‐H) barrier is prepared through photo‐controlled cross‐linking of reactive alkenyl groups. This degradable hydrogel demonstrates favorable rheological properties, light‐controlled unilateral adhesion properties, biocompatibility, anti‐fibrin adhesion, and anti‐cell adhesion properties in vitro. Comprehensive regulation of the fibrinolysis balance toward non‐adhesion is conformed in a rat model after intra‐abdominal surgery via anti‐autoinflammatory response, intestinal wall integrity repair, and Tissue plasminogen activator (t‐PA) and plasminogen activator inhibitor‐1 (PAI‐1) balance adjustment. Notably, the 14th day anti‐adhesion effective rate is 100%, indicating its significant potential in clinical applications for postoperative anti‐adhesion.

Abstract Colon cancer (CC) is a prevalent malignant tumor of the gastrointestinal tract and ranks among the leading causes of death in cancer patients worldwide. Cucurbitacin, a group of tetracyclic triterpenoids widely found in Cucurbitaceae plants, exhibits diverse pharmacological activities. However, the pharmacological activity of cucurbitacin C (CuC), a cucurbitacin derivative exclusively present in cucumbers, remains unclear. To investigate CuC's action targets and potential targets for CC, we utilized a database to obtain relevant information. Additionally, we identified differentially expressed genes in CC patients from The Cancer Genome Atlas and discovered 64 crossover targets formed through the intersection of drug‐disease targets. Through the construction of a protein‐protein interaction network, we identified 20 central genes. Enrichment analysis revealed that the cross‐targets were significantly enriched in four signaling pathways, namely, the PI3K‐Akt, Ras, MAPK, and IL‐17 signaling pathways. Correlation and expression analysis of the enriched central genes led to the identification of 7 key targets, among which matrix metalloproteinases (MMP)‐1, MMP‐3, and MMP‐13 demonstrated a significant association with poor prognosis in patients. Furthermore, we validated the network pharmacology results with in vitro and in vivo experiments. CuC can effectively inhibit the proliferation and migration of HCT‐116. CuC also can suppress the colon tumor growth in vivo, while reducing the expression of placental growth factor, MMP‐1, MMP‐3, MMP‐9, and MMP‐13 both in vitro and in vivo, consistent with the predicted results. Together, our results demonstrated that CuC holds promise as a potential agent for CC treatment.

Abstract Androgenetic alopecia (AGA) is one of the most common chronic skin diseases caused by the destruction of androgens in the body. It is caused by the excessive deposition of dihydrotestosterone around the hair follicle, resulting in hair follicle atrophy and hair cell apoptosis. It causes great anxiety and psychological distress to patients and affects sexual function in severe cases. As traditional Chinese herbs, ginsenosides have been proven to possess various pharmacological activities. Ginsenoside CK is one of the main ginsenosides, but its role and molecular mechanism in treating AGA remain unclear. Here, we found that ginsenoside CK intervention significantly reduced back hair loss in AGA mice, improved sexual organ damage and hair follicle cell apoptosis, and promoted hair growth in AGA mice. Ginsenoside CK treatment inhibited p53 expression, reduced the apoptosis of hair follicle cells induced by hormone deposition, activated the Wnt/β‐catenin cell proliferation signaling pathway, increased the level of vascular endothelial growth factor, promoted cell proliferation, and improved the atrophy of hair follicle tissue. Ginsenoside CK treatment also reduced testosterone levels in AGA mice, improved testicular tissue inflammation, and restored normal hormone metabolism in AGA mice. Our results indicated that ginsenoside CK reduced hair follicle cell apoptosis, promoted proliferation and development, and prolonged the hair growth cycle by regulating the Wnt and p53 signaling pathways, indicating the potential value of ginsenoside CK as a natural therapeutic agent for AGA.

Abstract Alopecia is a common chronic skin disease, which can be categorized as androgenetic alopecia (AGA), scarring line alopecia, genetic alopecia, and chemical alopecia due to the different reasons. Among which AGA caused by metabolism of the androgen system accounts for the majority. Due to the high prevalence of AGA and the lack of an effective cure, the urgent search for a safe and effective anti‐AGA drug has been our aim. With the advantages of its own wide source and low toxicity and side effects, the use of natural bioactive compounds and their extracts in the treatment of AGA has been a research hotspot. The objective of this work is to compile and synthesize experimental findings on natural bioactive compounds that possess the potential to alleviate AGA. On the basis of the known pathogenesis of AGA, combined with the target analysis of AGA by network pharmacology, identify natural bioactive compounds and their signaling pathways for the treatment of alopecia and hair growth promotion, and select representative hotspot compounds, to reveal their specific mechanisms and abstract the commonalities. Based on previous extensive research, hundreds of AGA targets (e.g., Wnt, TGF, and VEGF) closely regulate neogenesis, tissue development, and vascular function, to collect and summarize compounds such as ginseng, baicalein, curcumin, and so on, which have great potential to improve hair growth. Our work will inspire future research based on their mechanisms of action, providing more complete evidence and ideas for the feasibility of developing natural anti‐AGA drugs.

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.

Vascular endothelial growth factor (VEGF) plays a vital role in promoting attachment and proliferation of endothelial cells, and induces angiogenesis. In recent years, much research has been conducted on the functionalization of tissue engineering scaffolds with VEGF or a VEGF-mimetic peptide to promote angiogenesis. However, most chemical reactions are nonspecific and require organic solvents, which can compromise control over functionalization and alter peptide/protein activity. An attractive alternative is the fabrication of functionalizable electrospun fibers, which can overcome these hurdles. In this study, we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly (ε-caprolactone) (PCL) fibrous scaffolds with varying amounts of a functional PCL-diacrylate (PCL-DA) polymer. 30% PCL-DA was selected due to homogeneous fiber morphology. A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction. 7-Mercapto-4-methylcoumarin, RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction on the fibrous scaffolds. Tensile strength and elastic modulus of the 30% PCL-DA fibrous scaffolds were significantly increased after the reaction. Conjugation of the 30% PCL-DA fibrous scaffolds with the VEGF peptide increased the surface water wettability of the scaffolds. Patterned structures could be obtained after using a photomask on the fibrous film. Moreover, in vitro studies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of the VEGF receptor and enhanced HUVECs survival, proliferation and adhesion. A chick chorioallantoic membrane (CAM) assay further indicated that the VEGF peptide functionalized scaffolds were able to promote angiogenesis in vivo. These results show that scaffold functionalization can be controlled via a simple polymer mixing approach, and that the functionalized VEGF peptide-scaffolds have potential for vascular tissue regeneration.

Alzheimer's disease (AD) is a common neurodegenerative disease, which seriously impairs human health and life. At present, scientists have proposed more than a dozen hypotheses about the pathogenesis of AD, including the tau propagation hypothesis. However, the exact ultimate pathogenic factor of AD remains unknown. Based on the current hypotheses, some anti-AD drugs (e.g., donepezil and Ketamine) have been developed and used in clinical treatment, which fall into two main categories, acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonists, the former representative drug is donepezil, and the latter representative drug is memantine. Since these drugs have undesirable side effects, it is necessary to find safer alternatives for AD treatment. Interestingly, dietary phytochemicals have the advantages of wide source, safety, and high biological activity, which is the natural route for screening anti-AD drugs. In this study, several representatives’ dietary phytochemicals with anti-AD effect, including resveratrol, lycopene, gallic acid, berberine, ginsenoside Rg1, pseudoginsenoside-F11, ginsenoside Rh2, artemisinin, and torularhodin were selected from the published data over the last 10 years and their potential molecular mechanisms and clinical applications reviewed in the treatment of AD.

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

One of the most effective therapeutic proposals for type 2 diabetes mellitus (T2DM) is regulation of postprandial blood glucose (PBG) level by inhibiting α-glucosidases. In this study, we firstly investigated the influence of ginsenoside Rg1 (Rg1) on activity of α-glucosidase in vitro. The results revealed that Rg1 had a reversible inhibition on α-glucosidase activity in an uncompetitive manner. Fluorescence spectrum and circular dichroism (CD) analysis indicated that the stable complex between Rg1 and α-glucosidase was mainly formed by hydrogen bonds and hydrophobic forces. In addition, the anti-hyperglycemic effect of Rg1 was confirmed by the sucrose tolerance test in normal and db/db mice. Caco-2 monolayer cell model further emphasized that decreasing effect of Rg1 on PBG may be achieved by reducing glucose uptake and transport which is accounted for inhibition of α-glucosidase. Taken together, those results suggested that Rg1 may be used as a promising α-glucosidase inhibitor to decrease PBG.

Abstract Flexible electronics are playing an increasingly important role in human health monitoring and healthcare diagnosis. Strong adhesion on human tissue would be ideal for reducing interface resistance and motion artifacts, but arising problems such as skin irritation, rubefaction, and pain upon device removal have hampered their utility. Here, inspired by the temperature reversibility of hydrogen bonding, a skin-friendly conductive hydrogel with multiple-hydrogen bonds was designed by using biocompatible poly(vinyl alcohol) (PVA), phytic acid (PA), and gelatin (Gel). The obtained PVA/PA/Gel (PPG) hydrogel with temperature-triggered tunable mechanic could reliably adhere to skin and detect electrophysiological signals under a hot compress while be readily removed under a cool compress. Furthermore, the additional advantages of transparency, breathability, and antimicrobial activity of the PPG hydrogel ensure its long-time wearable value on the skin. It is both environmentally friendly and cost saving for the waste PPG hydrogel during production can be recycled based on their reversible physical bonding. The PPG hydrogel sensor is expected to have good application prospects to record electrophysiological signals in human health monitoring.

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.

Bacterial infection, tissue hypoxia and inflammatory response can hinder the infected wound repair process. To mitigate the above issues, tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets (MoS2@TA/Fe NSs) with dual enzyme activities were developed and anchored to a multifunctional hydrogel. The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy (PTT), glutathione (GSH) loss, and the peroxidase (POD)-like activity (catalyse H2O2 into ·OH under acid condition) of MoS2@TA/Fe NSs. Benefitting from the catalase (CAT)-like activity, the hydrogel could decompose H2O2 into O2 at neutral pH to relieve hypoxia and supply adequate O2. POD-like activity was mainly attributed to MoS2 NSs, while CAT-like activity was primarily due to TA/Fe complex. Moreover, MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species (ROS) and reactive nitrogen species (RNS) under neutral environment to maintain the balance of antioxidant systems and prevent inflammation. In addition, the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA. TA retained partial phenolic hydroxyl groups, which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels. Due to the dynamic boron ester bonds between polyvinyl alcohol (PVA), dextran (Dex), MoS2@TA/Fe, and borax, the hydrogel demonstrated fast self-healing and rapid shape adaptability. This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound, ensuring that it achieved its functions with maximum efficiency. The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.

Abstract In addition to oxidative stress and impaired angiogenesis, the overexpression of metalloproteinases (MMPs) and proinflammatory cytokines, which are promoted by hyperglycemia, causes chronic inflammation in diabetic wounds. Herein, TA‐siRNA nanogels are prepared for the first time on the basis of the self‐assembling interaction between tannic acid (TA) and short interfering RNA (siRNA). The efficient, biodegradable nanogels are cross‐linked with poly(vinyl alcohol) (PVA), human‐like collagen (HLC), TA, and borax to prepare adaptive, conductive PHTB (TA‐siRNA) hydrogels. In response to high levels of reactive oxygen species (ROS), the ROS‐responsive borate ester bonds in the hydrogels are oxidized and broken, and TA‐siRNA nanogels are released into cells to reduce the expression of the MMP‐9. Moreover, the TA and HLC promote collagen expression, reduce inflammation, and ROS level. It is found that electrical stimulation (ES) promotes the in vivo release of TA‐siRNA nanogels from PHTB (TA‐siRNA) hydrogels and endocytosis of the nanogels. The combination therapy using ES and PHTB (TA‐siRNA) hydrogels accelerates the healing of diabetic wounds by reducing the levels of ROS and MMP‐9 and promoting the polarization of macrophages, production of collagen, and angiogenesis. This study provides insights on the design of functional gene‐delivery and efficient therapeutic strategies to promote the repair of diabetic chronic wounds.

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.

Noncompressible wounds resulting from accidents and gunshots are typically associated with excessive bleeding, slow wound healing, and bacterial infection. Shape-memory cryogel presents great potential in controlling the hemorrhaging of noncompressible wounds. In this research, a shape-memory cryogel was prepared using a Schiff base reaction between alkylated chitosan (AC) and oxidized dextran (ODex) and then incorporated with a drug-laden and silver-doped mesoporous bioactive glass (MBG). Hydrophobic alkyl chains enhanced the hemostatic and antimicrobial efficiency of the chitosan, forming blood clots in the anticoagulated condition, and expanding the application scenarios of chitosan-based hemostats. The silver-doped MBG activated the endogenous coagulation pathway by releasing Ca2+ and prevented infection through the release of Ag+. In addition, the proangiogenic desferrioxamine (DFO) in the mesopores of the MBG was released gradually to promote wound healing. We demonstrated that AC/ODex/Ag-MBG DFO(AOM) cryogels exhibited excellent blood absorption capability, facilitating rapid shape recovery. It provided a higher hemostatic capacity in normal and heparin-treated rat-liver perforation-wound models than gelatin sponges and gauze. The AOM gels simultaneously promoted infiltration, angiogenesis, and tissue integration of liver parenchymal cells. Furthermore, the composite cryogel exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Thus, AOM gels show great promise for clinical translation in treating lethal, noncompressible bleeding and the promotion of wound healing.

Worldwide, drug-induced acute liver failure is associated with a high rate of morbidity and mortality. Acetaminophen (APAP), a widely used analgesic, is one of the most common causes of acute liver injury. The purpose of this study was to determine the protective effect of protopanaxatriol-type saponin (PTS) against APAP-induced liver injury and to elucidate the mechanisms underlying this effect. Mice were pretreated with PTS via gavage for 7 days prior to receiving APAP. The results indicated that PTS was highly effective in preventing hepatotoxicity caused by APAP. Meanwhile, pretreatment with PTS resulted in a decrease in inflammation and oxidative stress. Furthermore, PTS reversed the histological change and reduced hepatic injury. Additionally, PTS inhibited the expression of proteins associated with APAP induced hepatic apoptosis in the liver. Taken together, our findings indicated that PTS protected against liver injury caused by APAP by alleviating oxidative stress, inflammation, and apoptosis via the ROS-mediated JNK pathway. Our findings suggest that PTS may have the potential as a novel therapeutic agent for APAP-induced liver injury.

Ginseng is a widely cultivated perennial plant in China and Korea. Ginsenoside Rk3 is one of the major active components of ginseng and is a promising candidate to regulate skin pigments and exert anti-photoaging effects on skin physiology. Ginsenoside Rk3 was mixed with a cream (G-Rk3 cream) and smeared on the skin of mice. Then, the mice were exposed to ultraviolet (UV) A (340 nm and 40 W) and UVB (313 nm and 40 W) radiation. Special attention was given to the anti-photoaging and anti-inflammatory effects of ginsenoside Rk3 on the mouse skin. Macroscopic evaluation indicated that the mouse dorsal skin looked smooth and plump even under UV irradiation for 12 weeks. Pathological analysis indicated that there was no obvious photoaging or inflammation in the mouse skin that was treated with the G-Rk3 cream. More healthy, intact, and neat collagen fibers were observed in mice treated with the G-Rk3 cream than in untreated mice. Further analysis proved that ginsenoside Rk3 could inhibit the decrease in water and hydroxyproline levels in skin tissues and the loss of superoxide dismutase and glutathione peroxidase activities in the blood. Moreover, ginsenoside Rk3 slowed or halted increases in malondialdehyde, matrix metalloproteinase (MMP)-1, and MMP-3 levels in the blood and levels of interleukin 1, interleukin 6, and tumor necrosis factor α in skin tissues. In conclusion, ginsenoside Rk3 plays a significant role in inhibiting photoaging and inflammation to protect skin health.

Ginsenosides have been reported to possess pharmacological effects, such as antioxidative, anti-inflammatory and antitumor effects. Nevertheless, little has been reported about the anti-breast cancer effects of ginsenoside Rk1 (Rk1). In this work, we explored the anti-breast cancer effects of Rk1. The results suggested that Rk1 suppressed cell growth, colony formation, and triggered S phase arrest. Rk1 also triggered ROS overproduction, reduced mitochondrial membrane potential and induced apoptosis. Moreover, the PTEN/PI3K/Akt/mTOR pathway was involved in Rk1-induced apoptosis. Treatment with Z-VAD-FMK, LY294002 and N-acetylcysteine further illustrated that Rk1 induced apoptosis in MCF-7 cells through ROS-mediated PTEN/PI3K/Akt/mTOR signaling pathway. Furthermore, in xenograft nude mice model, Rk1 treatment dramatically suppressed tumor growth and caused no obvious injuries to major organs. Taken together, the results of this study demonstrated, for the first time, the anticancer efficacy and mechanism of Rk1 in MCF-7 cells, providing basic evidence supporting Rk1 as a potential anti-breast cancer agent.

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.

Lung cancer has a high mortality rate and is very common. One of the main reasons for the poor prognosis of patients with lung cancer is the high incidence of metastasis. Ginsenoside Rh3, a rare ginsenoside extracted from Panax notoginseng, exhibits excellent anti-inflammatory and anti-tumor effects. Nonetheless, the inhibitory potential of Rh3 against lung cancer remains unknown. The target genes of Rh3 were screened by the PharmMapper database; the proliferation of lung cancer cells was detected by MTT assay; the migration and invasion of cells were detected by the Transwell method; and the expression of extracellular signal-regulated kinase (ERK) and EMT-related proteins in vivo and in vitro were detected by Western blotting. In addition, we established a lung metastasis model in nude mice using A549 cells to assess the effect of Rh3 on NSCLC tumor metastasis in vivo. Our findings suggest that Rh3 significantly inhibited lung cancer metastasis both in vivo and in vitro. It was determined by flow cytometry analysis that Rh3 notably inhibited cell proliferation by blocking the G1 phase. In addition, Rh3 inhibited metastasis in lung cancer cells and regulated the expression of metastasis-related proteins under hypoxia. Mechanistic studies suggested that Rh3 targeted ERK to inhibit lung cancer metastasis. The ERK inhibitor U0126 or siRNA-mediated knockdown of ERK had an enhanced effect on Rh3’s ability to inhibit lung cancer metastasis. The studies revealed that the inhibitory effect of Rh3 on the metastatic ability of lung cancer cells may be supported by ERK-related signaling pathways.

Type 2 diabetes mellitus (T2DM) is a systemic metabolic disorder that has become a major threat to public health. Ginsenoside Rg5 (Rg5) has a putative hypoglycemic effect, but its potential mechanism remains unclear. Here, we found that Rg5 not only reduced glycolipid parameters (FBG, TC, TG, and LDL-C), relieved inflammation (TNF-α, IL-6, and IL-1β), improved hepatic lipid accumulation, and repaired pancreas damage but also increased hepatic glycogen storage by reducing the expression of GSK-3β and increasing the expression of GS in diabetic db/db mice. Furthermore, Rg5 significantly up-regulated the phosphorylation of IRS1, PI3K, and AKT to enhance insulin transduction in liver tissues. These results indicated that Rg5 could alleviate hepatic insulin resistance and improve glucose intolerance by activating the IRS1/PI3K/AKT/GSK3β-GS signaling pathway. Together, Rg5 provide a potential treatment for T2DM and its related metabolic disorders.

The annual global mortality rate of cancer has increased dramatically. Although various therapies are used for cancer, the results have not been satisfactory. Chemotherapy is currently the most common treatment option. However, serious side effects and drug resistance impede the therapeutic efficacy of chemotherapeutic drugs. Increasing evidence has shown that ginsenosides as a type of phytochemicals play an important role in the prevention and treatment of cancers, such as colon cancer, cervical cancer, ovarian cancer, breast cancer, lung cancer, pancreatic cancer, bladder cancer, esophageal cancer, and bone cancer. Ginsenosides block a variety of enzymes required for tumor growth, which regulate an array of cell progression, such as nitric oxide synthase activity, protein kinase activity, epidermal growth factor receptor intrinsic kinase activity, and nuclear factor-kappaB activity. Ginsenosides also inhibit lipid peroxidation and the production of reactive oxygen species. Thus, ginsenosides can be used as an adjuvant to conventional cancer therapies to improve efficacy and/or reduce side effects through synergistic activity. In this review, we summarized the latest research advances of the anticancer effects of ginsenosides and their potential mechanisms.

The aim of this study is to investigate the effect of kiwifruit seed oil (KSO) on inflammation and hepatic fat metabolism in high-fat diet (HFD)-induced C57BL/6 obese mice for 12 consecutive weeks by oral intervention. The results showed that KSO supplementation inhibited the body weight gain, decreased fasting blood glucose and insulin levels, and alleviated glucose and insulin tolerance in obese mice. KSO supplementation reduced the hepatic fat accumulation by inhibiting the levels of triglyceride, total cholesterol and adipose hollow space in HFD-induced mice liver tissues. Additionally, KSO administration down-regulated the expression of inflammation-related cytokines (TNF-α, IL-1β and IL-6) and lipid synthesis related genes (PPAR-γ and FAS), while up-regulated the expression of fatty acid β oxidation-related genes (PPAR-α, CPT1a and CPT1b) and thermogenesis-related gene (UCP2) in liver both in transcriptional and translational levels. Overall, our results implicate that KSO as a potential dietary supplement for the prevention of obesity.

It is well known that ginsenosides—major bioactive constituents of Panax ginseng—are attracting more attention due to their beneficial pharmacological activities. Ginsenoside Rd, belonging to protopanaxadiol (PPD)-type ginsenosides, exhibits diverse and powerful pharmacological activities. In recent decades, nearly 300 studies on the pharmacological activities of Rd—as a potential treatment for a variety of diseases—have been published. However, no specific, comprehensive reviews have been documented to date. The present review not only summarizes the in vitro and in vivo studies on the health benefits of Rd, including anti-cancer, anti-diabetic, anti-inflammatory, neuroprotective, cardioprotective, ischemic stroke, immunoregulation, and other pharmacological effects, it also delves into the inclusion of potential molecular mechanisms, providing an overview of future prospects for the use of Rd in the treatment of chronic metabolic diseases and neurodegenerative disorders. Although biotransformation, pharmacokinetics, and clinical studies of Rd have also been reviewed, clinical trial data of Rd are limited; the only data available are for its treatment of acute ischemic stroke. Therefore, clinical evidence of Rd should be considered in future studies.

The adsorption capacity of bentonite clay for heavy metal removal from wastewater can be significantly enhanced by a high loading of chitosan on the surface. In order to enhance the chitosan loading, we tested activating bentonite clay by three methods prior to chitosan loading: sulfuric acid, calcination, and microwave treatments. Meanwhile, several parameters during chitosan loading, namely the initial chitosan concentration, stirring speed, reaction time, temperature, and pH value were investigated. Our results indicate that chitosan is attached to bentonite clay through intercalation and surface adsorption according to X-ray Diffraction (XRD), Scanning Eelectron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR) analyses. The maximum chitosan loading on 200-mesh raw bentonite clay (126.30 mg/L) was achieved under the following conditions: the initial chitosan concentration of 1000 mg/L, the stirring speed of 200 rpm, pH of 4.9, 60 min of reaction time, and temperature of 30 °C. The chitosan loading was further increased to 256.30, 233.70, and 208.83 mg/g, when using bentonite clay activated through 6 min of microwave irradiation (800 W), 10 % sulfuric acid treatment, and calcinations at 600 °C, respectively. When the chitosan loading was increased from 34.76 to 233.7 mg/g, the removal percentages of Cu(II), Cr(VI), and Pb(II) were improved, respectively from 78.90 to 95.5 %, from 82.22 to 98.74 %, from 60.09 to 86.18 %.

Hepatocellular carcinoma (HCC) is a kind of malignant tumor with high morbidity and mortality rates worldwide. Epithelial–mesenchymal transformation (EMT) is crucial for HCC progression and prognosis. Characteristics of the tumor microenvironment, such as hypoxia, and excessive activation of the NF-κB signaling pathway have been identified as the key inducers of EMT in HCC. In our study, we verified the crosstalk between HIF-1α signaling and NF-κB pathway and their effects on EMT in HCC cells. The results show that CoCl2-induced hypoxia could promote IκB phosphorylation to activate NF-κB signaling and vice versa. Moreover, we found that ginsenoside CK, a metabolite of protopanaxadiol saponins, could inhibit the proliferation and colony formation of different HCC cell lines. Furthermore, ginsenoside CK could impair the metastatic potential of HCC cell lines under hypoxic conditions. Mechanistically, ginsenoside CK suppressed HIF-1α/NF-κB signaling and expression level of EMT-related proteins and cytokines in hypoxia-induced or TNFα-stimulated HCC cell lines. An in vivo study revealed that the oral delivery of ginsenoside CK could inhibit the growth of xenograft tumors and block HIF-1α and NF-κB signaling as well as EMT marker expression. Our study suggests that ginsenoside CK is a potential therapy for HCC patients that functions by targeting the HIF-1α/NF-κB crosstalk.

Colon cancer is one of the most lethal malignancies worldwide. Berberine has been found to exert potential anti-colon cancer activity in vitro and in vivo, although the detailed regulatory mechanism is still unclear. This study aims to identify the underlying crucial proteins and regulatory networks associated with berberine treatment of colon cancer by using proteomics as well as publicly available transcriptomics and tissue array data. Proteome profiling of berberine-treated colon cancer cells demonstrated that among 5130 identified proteins, the expression of 865 and 675 proteins were changed in berberine-treated HCT116 and DLD1 cells, respectively. Moreover, 54 differently expressed proteins that overlapped in both cell lines were mainly involved in mitochondrial protein synthesis, calcium mobilization, and metabolism of fat-soluble vitamins. Finally, GTPase ERAL1 and mitochondrial ribosomal proteins including MRPL11, 15, 30, 37, 40, and 52 were identified as hub proteins of berberine-treated colon cancer cells. These proteins have higher transcriptional and translational levels in colon tumor samples than that of colon normal samples, and were significantly down-regulated in berberine-treated colon cancer cells. Genetic dependency analysis showed that silencing the gene expression of seven hub proteins could inhibit the proliferation of colon cancer cells. This study sheds a light for elucidating the berberine-related regulatory signaling pathways in colon cancer, and suggests that ERAL1 and several mitochondrial ribosomal proteins might be promising therapeutic targets for colon cancer.

The rare ginsenoside Rk3 is a bioactive component derived from ginseng and Panax notoginseng that has been proven to possess anti-lung cancer activity. However, the effect of Rk3 on human esophageal cancer has not yet been reported. In this study, we aimed to explore its anticancer curative effect and potential molecular mechanisms in the Eca109 and KYSE150 cell lines. We found that Rk3 was able to significantly repress cell proliferation and colony formation in both Eca109 and KYSE150 cells in vitro. In the KYSE150 xenograft model, Rk3 obviously inhibited tumor growth and exhibited little toxicity in organs. Moreover, Rk3 could trigger G1 phase arrest and induce apoptosis and autophagy. Interestingly, apoptosis induced by Rk3 could be partly abrogated by 3-MA (an autophagy inhibitor), implying that autophagy could enhance apoptosis. Further studies indicated that pretreatment with the Akt inhibitor GSK690693 or the mTOR inhibitor rapamycin promoted Rk3-induced apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway is related to Rk3-induced apoptosis and autophagy. In conclusion, the present study is the first to clarify that Rk3 can inhibit Eca109 and KYSE150 cell proliferation through activating apoptosis and autophagy by blocking the PI3K/Akt/mTOR pathway, suggesting that Rk3 may be a promising antitumor agent for esophageal cancer. In addition, this study provides ideas and an experimental basis for further research on the anti-esophageal cancer effects of the ginsenoside Rk3 and its mechanism.

Ginsenoside is a major active component of ginseng, which exhibits various pharmacological properties such as hepatoprotection, tumor suppression and diabetes resistance. In this study, the anti-diabetic effects of protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins were explored and compared in high-fat diet/streptozocin-induced type 2 diabetes mellitus (T2DM) mice. Our results showed that low or high dose (50 mg/kg bodyweight or 150 mg/kg bodyweight) PPD and PPT significantly reduced fasting blood glucose, improved glucose tolerance and insulin resistance in T2DM mice. PPD and PPT also regulated serum lipid-related markers such as reduced total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol in T2DM mice. In addition, PPD and PPT dramatically ameliorated the inflammatory responses by suppressing the secretion of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6 in serum level and gene expression in liver level, and improved the antioxidant capacity by increasing the superoxide dismutase and decreasing malondialdehyde levels in the serum of T2DM mice. Moreover, the anti-diabetic effect of PPD and PPT appeared to be partially mediated by the suppression of hepatic metabolism genes expression such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, as well as facilitating lipid metabolism genes expression such as microsomal TG transfer protein in the liver tissues of T2DM mice. Taken together, our results indicated that PPD and PPT might potentially act as natural anti-diabetic compounds to be used for preventing and treating the T2DM and its complications in the future.

Designing the “ideal” hydrogel/matrix which can load bone morphogenetic protein-2 (BMP-2) in a low dose and with a sustained release is the key for its successful therapeutic application to enhance osteogenesis. The current use of natural collagen sponges as hydrogel/matrix is limited due to the collagen matrix showing weak mechanical strength and unmanageable biodegradability. Furthermore, the efficiency and safe dose usage of the BMP-2 has never been seriously considered other than purely chasing the lowest dose usage and extended-release time. In this paper, we customized a novel enzymatically cross-linked recombinant human-like collagen (HLC) sponge with low immunogenicity, little risk from hidden viruses, and easy production. We obtained a unique vertical pore structure and the porosity of the HLC, which are beneficial for Mesenchymal stem cells (MSCs) migration into the HLC sponge and angiopoiesis. This HLC sponge loading with low dose BMP-2 (1 µg) possessed high mechanical strength along with a burst and a sustained release profile. These merits overcome previous limitations of HLC in bone repair and are safer and more sensitive than commercial collagens. For the first time, we identified that a 5 µg dose of BMP-2 can bring about the side effect of bone overgrowth through this sensitive delivery system. Osteoinduction of the HLC-BMP sponges was proved by an in vivo mouse ectopic bone model and a rat cranial defect repair model. The method and the HLC-BMP sponge have the potential to release other growth factors and aid other tissue regeneration. Additionally, the ability to mass-produce HLC in our study overcomes the current supply shortage, which limits bone repair in the clinic.

Kiwi fruit (Actinidia chinensis Planch.) seeds, present as a by-product in the food and pharmaceutical industries, remain underutilized. In this study the extraction conditions for the maximum recovery of total phenolic content (TPC) with high DPPH scavenging capacities (DPPHsc) were analyzed for kiwi fruit seed polyphenols (KSP) by response surface methodology. The optimal conditions for the highest yield of TPC (53.73 mg GAE/g DW) with 63.25% DPPHsc was found by using an extraction time of 79.65 min with an eluent containing 59.45% acetone at 38.35 °C and a 1:11.52 (w/v) solid/liquid ratio. Compared with butyl hydroxy toluene (BHT), a synthetic antioxidant, the extracted KSP showed higher DPPHsc and ferric reducing antioxidant power, but was less efficient than grape seed polyphenols extracted under the same optimum conditions. We also showed that the extracted KSP exhibited strong anti-inflammatory activities by suppressing the secretion of pro-inflammatory cytokines like interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) in lipopolysaccharides (LPS)-induced RAW 264.7 cells. High performance liquid chromatography-electrochemical detector (HPLC-ECD) analysis of the extracted KSP under optimized conditions revealed that the extract was mainly composed of five polyphenolic compounds. Our work showed the development of an optimal extraction process of the KSP, which presented excellent antioxidant and anti-inflammatory activities, indicating that kiwi fruit seeds may further be utilized as a potential source of natural biological active compounds.