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Bioactive Materials Nov 2023Tumor microenvironment (TME) plays an important role in the tumorigenesis, proliferation, invasion and metastasis. Thereby developing synergistic anticancer strategies...
A metal ions-mediated natural small molecules carrier-free injectable hydrogel achieving laser-mediated photo-Fenton-like anticancer therapy by synergy apoptosis/cuproptosis/anti-inflammation.
Tumor microenvironment (TME) plays an important role in the tumorigenesis, proliferation, invasion and metastasis. Thereby developing synergistic anticancer strategies with multiple mechanisms are urgent. Copper is widely used in the treatment of tumor chemodynamic therapy (CDT) due to its excellent laser-mediated photo-Fenton-like reaction. Additionally, copper can induce cell death through cuproptosis, which is a new modality different from the known death mechanisms and has great promise in tumor treatment. Herein, we report a natural small molecules carrier-free injectable hydrogel (NCTD Gel) consisted of Cu-mediated self-assembled glycyrrhizic acid (GA) and norcantharidin (NCTD), which are mainly governed by coordination and hydrogen bonds. Under 808 nm laser irradiation, NCTD Gel can produce reactive oxygen species (ROS), consume glutathione (GSH) and overcome hypoxia in TME, leading to synergistically regulate TME via apoptosis, cuproptosis and anti-inflammation. In addition, NCTD Gel's CDT display high selectivity and good biocompatibility as it relies on the weak acidity and HO overexpression of TME. Notably, NCTD Gel's components are originated from clinical agents and its preparation process is easy, green and economical, without any excipients. This study provides a new carrier-free hydrogel synergistic antitumor strategy, which has a good prospect in industrial production and clinical transformation.
PubMed: 37456579
DOI: 10.1016/j.bioactmat.2023.06.018 -
Nutrients Jul 2023Hyperhomocysteinemia (HHcy) worsens cardiovascular outcomes by impairing vascular function and promoting chronic inflammation via release of danger-associated molecular...
Hyperhomocysteinemia (HHcy) worsens cardiovascular outcomes by impairing vascular function and promoting chronic inflammation via release of danger-associated molecular patterns, such as high-mobility group box-1 (HMGB-1). Elevated levels of HMGB-1 have recently been reported in patients with HHcy. Therefore, targeting HMGB-1 may be a potential therapy to improve HHcy-induced cardiovascular pathologies. This study aimed to further elucidate HMGB-1's role during acute HHcy and HHcy-induced atherogenesis and to determine if inhibiting HMGB-1 with glycyrrhizic acid (Glyz) improved vascular function. Male New Zealand White rabbits ( = 25) were placed on either a standard control chow (CD; = 15) or atherogenic diet (AD; = 10) for 4 weeks. Rabbit serum and Krebs taken from organ bath studies were collected to quantify HMGB-1 levels. Isometric tension analysis was performed on abdominal aorta (AA) rings from CD and AD rabbits. Rings were incubated with homocysteine (Hcy) [3 mM] for 60 min to induce acute HHcy or rhHMGB-1 [100 nM]. Vascular function was assessed by relaxation to cumulative doses of acetylcholine. Markers of vascular dysfunction and inflammation were quantified in the endothelium, media, and adventitia of AA rings. HMGB-1 was significantly upregulated in serum ( < 0.0001) and Krebs ( < 0.0001) after Hcy exposure or an AD. Incubation with Hcy ( < 0.0001) or rhHMGB-1 ( < 0.0001) and an AD ( < 0.0001) significantly reduced relaxation to acetylcholine, which was markedly improved by Glyz. HMGB-1 expression was elevated ( < 0.0001) after Hcy exposure and AD ( < 0.0001) and was normalized after Glyz treatment. Moreover, markers of vascular function, cell stress and inflammation were also reduced after Glyz. These results demonstrate that HMGB-1 has a central role during HHcy-induced vascular dysfunction and inhibiting it with Glyz could be a potential treatment option for cardiovascular diseases.
Topics: Male; Rabbits; Animals; Acetylcholine; Glycyrrhizic Acid; Atherosclerosis; Inflammation; HMGB Proteins; Hyperhomocysteinemia; Homocysteine
PubMed: 37513606
DOI: 10.3390/nu15143186 -
Frontiers in Pharmacology 2023Since the first 70 years of reporting cancer chemotherapy, malignant tumors have been the second most common cause of death in children and adults. Currently, the... (Review)
Review
Since the first 70 years of reporting cancer chemotherapy, malignant tumors have been the second most common cause of death in children and adults. Currently, the commonly used anti-cancer methods include surgery, chemotherapy, radiotherapy, and immunotherapy. Although these treatment methods could alleviate cancer, they lead to different forms of side effects and have no particularly significant effect on prolonging the patients' life span. Glycyrrhizic acid (GL), a native Chinese herbal extract, has a wide range of pharmacological effects, such as anti-cancer, anti-inflammatory, antioxidant, and immune regulation. In this review, the anti-cancer effects and mechanisms of GL are summarized in various cancers. The inhibition of GL on chemotherapy-induced side effects, including hepatotoxicity, nephrotoxicity, genotoxicity, neurotoxicity and pulmonary toxicity, is highlighted. Therefore, GL may be a promising and ideal drug for cancer therapy.
PubMed: 37649893
DOI: 10.3389/fphar.2023.1265172 -
PloS One 2023Glycyrrhetinic acid, a drug with anti-inflammatory effects, enhanced the activity of antipsoriatic efficacy. In this research, an ointment with glycyrrhetinic acid was...
Glycyrrhetinic acid, a drug with anti-inflammatory effects, enhanced the activity of antipsoriatic efficacy. In this research, an ointment with glycyrrhetinic acid was prepaired as the major component and several other herbal monomers (astilbin, osthole, and momordin Ic) have antipsoriatic activity as minor components. Then an Imiquimod-induced psoriasis-like mouse model was established and the damaged skin condition of the administered group, the changes in the spleen index and the secretion of inflammatory factors in mouse skin were observed. Calcipotriol ointment was used as a positive control to compare the efficacy. Glycyrrhizic acid compound ointment significantly improved imiquimod-induced psoriasis in mice and reduced the secretion of TNF-α, IL-12, IL-17, and IL-23 in mouse skin, and showed a stronger therapeutic effect than calcipotriol ointment. Calcipotriol ointment did not significantly alleviate imiquimod-induced splenomegaly and did not significantly reduce the expression of IL-17 and IL-23 in mouse skin. Glycyrrhetinic acid compound ointment was more effective than calcipotriol and was dose-dependent in the treatment of imiquimod-induced psoriatic dermatitis in mice. Meanwhile,calcipotriol was not suitable for the treatment of Imiquimod -induced psoriasis-like mice.
Topics: Animals; Mice; Glycyrrhizic Acid; Imiquimod; Interleukin-17; Ointments; Psoriasis; Glycyrrhetinic Acid; Interleukin-23
PubMed: 37643205
DOI: 10.1371/journal.pone.0290637 -
World Journal of Gastrointestinal... Jul 2023The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to...
BACKGROUND
The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to the prevention of this disease.
AIM
To explore the possible mechanism of glycyrrhizic acid (GA) and its therapeutic effect on HAEC.
METHODS
We developed a model of enteritis induced by trinitrobenzenesulfonic acid (TNBS) in zebrafish, and treated it with different concentrations of GA. We analyzed the effect of GA on the phenotype and inflammation of zebrafish.
RESULTS
After treatment with TNBS, the area of the intestinal lumen in zebrafish was significantly increased, but the number of goblet cells in the intestinal lumen was significantly reduced, but these did not increase the mortality of zebrafish, indicating that the zebrafish enteritis model was successfully developed. Different concentrations of GA protected zebrafish with enteritis. In particular, high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area, increased the number of goblet cells in the intestinal lumen, and reduced the levels of interleukin (IL)-1β and IL-8.
CONCLUSION
GA significantly reduced the intestinal luminal area, increased the number of intestinal goblet cells, and decreased IL-1β and IL-8 in zebrafish, and is important for prevention and control of HAEC.
PubMed: 37555121
DOI: 10.4240/wjgs.v15.i7.1317 -
Frontiers in Microbiology 2023Foot-and-mouth disease (FMD) is an extremely contagious viral disease that is fatal to young animals and is a major threat to the agricultural economy by reducing...
BACKGROUND
Foot-and-mouth disease (FMD) is an extremely contagious viral disease that is fatal to young animals and is a major threat to the agricultural economy by reducing production and limiting the movement of livestock. The currently commercially-available FMD vaccine is prepared using an inactivated viral antigen in an oil emulsion, with aluminum hydroxide [Al(OH)] as an adjuvant. However, oil emulsion-based options possess limitations including slow increases in antibody titers (up to levels adequate for defense against viral infection) and risks of local reactions at the vaccination site. Further, Al(OH) only induces a T helper 2 (Th2) cell response. Therefore, novel adjuvants that can address these limitations are urgently needed. Glycyrrhizic acid (extracted from licorice roots) is a triterpenoid saponin and has great advantages in terms of price and availability.
METHODS
To address the limitations of the currently used commercial FMD vaccine, we added glycyrrhizic acid as an adjuvant (immunostimulant) to the FMD bivalent (O PA2 + A YC) vaccine. We then evaluated its efficacy in promoting both innate and adaptive (cellular and humoral) immune reactions [using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs)] and (using mice and pigs).
RESULTS
Glycyrrhizic acid has been revealed to induce an innate immune response and enhance early, mid-, and long-term immunity. The studied bivalent vaccine with glycyrrhizic acid increased the expression of immunoregulatory genes such as pattern-recognition receptors (PRRs), cytokines, transcription factors, and co-stimulatory molecules.
CONCLUSION
Collectively, glycyrrhizic acid could have utility as a novel vaccine adjuvant that can address the limitations of commercialized FMD vaccines by inducing potent innate and adaptive immune responses.
PubMed: 38029108
DOI: 10.3389/fmicb.2023.1289065 -
Physical Chemistry Chemical Physics :... Jan 2024Bio- or plant-based surfactants are a sustainable and renewable alternative to replace synthetic chemicals for environmental, drugs and food applications. However, these... (Review)
Review
Bio- or plant-based surfactants are a sustainable and renewable alternative to replace synthetic chemicals for environmental, drugs and food applications. However, these "green" surfactants have unique molecular structures, and their self-assembly in water might lead to complex morphologies and unexpected properties. The micellization of saponin molecules, such as glycyrrhizic acid (GA), differs significantly from those of conventional synthetic surfactants, yet these differences are often overlooked. Saponins self-assemble in complex hierarchical helical morphologies similar to bile salts, rather than the expected globular, ellipsoidal and wormlike micelles. Here, we review two potential routes for molecular self-assembly of GA, namely kinetics of crystallization and thermodynamic equilibrium, focusing on their structure as a function of concentration. Some uncertainty remains to define which route is followed by GA self-assembly, as well as the first type of aggregate formed at low concentrations, thus we review the state-of-the-art information about GA assembly. We compare the self-assembly of GA with conventional linear surfactants, and identify their key similarities and differences, from molecular and chemical perspectives, based on the critical packing parameter (CPP) theory. We expect that this work will provide perspectives for the unclear process of GA assembly, and highlight its differences from conventional micellization.
Topics: Glycyrrhizic Acid; Surface-Active Agents; Molecular Structure; Micelles; Water
PubMed: 38196347
DOI: 10.1039/d3cp04835g -
European Journal of Pharmaceutical... Jan 2024Paeoniflorin (PF) and glycyrrhizic acid (GL) have skin beautifying effects of anti-inflammation, anti-oxidation, inhibition of melanin formation, and reduction of skin...
Paeoniflorin (PF) and glycyrrhizic acid (GL) have skin beautifying effects of anti-inflammation, anti-oxidation, inhibition of melanin formation, and reduction of skin pigmentation. To improve the transdermal permeability of PF and GL in transdermal drug delivery system (TDDS) and enhance their anti-melasma efficacy, PF-GL transethosome (PF-GL-TE) was prepared by ethanol injection method, and finally gelled with carbomer-940 to form PF-GL-TE gel. Consequently, the obtained PF-GL-TE is small and uniform, with an average particle size and a PDI value of about 167.9 nm and 0.102. PF-GL-TE gel showed sustained release behavior and high transdermal permeability in vitro release and transdermal tests. Meanwhile, PF-GL-TE gel played significant preventive effects on melasma induced by progesterone injection and ultraviolet radiation B (UVB) irradiation. According to the results of H&E staining and Masson staining of rat skin, PF-GL-TE gel can alleviate the skin inflammation of and reduce the loss of collagen fibers of back skin in the melasma model rats. Compared with the PF-GL mixture gel, PF-GL-TE gel significantly attenuated the oxidative damage of liver and skin by increasing the activity of SOD and reducing the content of MDA. The results of Western blot showed that PF-GL-TE gel might down-regulate melanin-related proteins expressions of MITF/TYR/TRP1 and TRP2 to prevent and treat melasma. These findings indicate that PF-GL-TE gel is an effective TDDS for delivering PF and GL into the skin, providing a promising preparation for effective prevention and treatment of melasma.
Topics: Rats; Animals; Glycyrrhizic Acid; Melanins; Ultraviolet Rays; Melanosis
PubMed: 38061662
DOI: 10.1016/j.ejps.2023.106664 -
Chinese Medicine Nov 2023Synovial neovascularization promotes rheumatoid arthritis (RA) progression. Baihu guizhi decoction (BHGZD) has a potential in restricting this pathological change of RA.
BACKGROUND
Synovial neovascularization promotes rheumatoid arthritis (RA) progression. Baihu guizhi decoction (BHGZD) has a potential in restricting this pathological change of RA.
PURPOSE
To identify bioactive compounds (BACs) of BHGZD and to elucidate the underlying mechanisms in restricting synovial neovascularization of RA.
METHOD
Through transcriptomic profiling, the chemical profiling of BHGZD and its effective transcriptomic profiling against RA were identified. Then, candidate targets and the corresponding BACs against synovial neovascularization were screened by "disease gene-drug target" interaction network analysis and in silico molecular docking. The binding affinities of candidate BAC-target pairs were verified using surface plasmon resonance, and the pharmacokinetic characteristics of BACs in vivo after BHGZD administration at different time points were detected by Ultra Performance Liquid Chromatography-Mass spectrum/Mass spectrum. After that, in vivo experiments based on adjuvant-induced arthritis (AIA-M) rats, and in vitro experiments based on human umbilical vein endothelial cells (HUVEC) and arthritic synovial fibroblasts (MH7A) were carried out to evaluate the pharmacological effects of BHGZD and the two-BACs-combination, and to verify the associated mechanisms.
RESULT
VEGFA/VEGFR2/SRC/PI3K/AKT signal axis was screened as one of the key network targets of BHGZD against synovial neovascularization in RA. Mangiferin (MG) and glycyrrhizic acid (GA) were identified as the representative BACs of BHGZD for their strong binding affinities with components of the VEGFA/VEGFR2/SRC/PI3K/AKT signal axis, and their high exposed quantity in vivo. Both BHGZD and the two-BAC combination of MG and GA were demonstrated to be effective in restricting disease severity, reducing synovial inflammation and decreasing the formation of vascular opacities in AIA-M rats, and also reducing the migrative and invasive activities of HUVEC and MH7A cells and attenuating the lumen formation ability of HUVEC cells significantly. Mechanically, both BHGZD and the two-BAC combination markedly reduced the expression of VEGFA in synovial tissues, the serum levels of VEGF and NO, and the enzymatic activity of eNOS, increased the content of endostatin, and also reversed the abnormal alterations in the VEGFA/VEGFR2/SRC/PI3K/AKT signal axis in vivo and in vitro.
CONCLUSION
MG and GA may be the representative BACs of BHGZD for restricting excessive synovial vascularization in RA via regulating VEGFA/VEGFR2/SRC/PI3K/AKT signal axis.
PubMed: 38037139
DOI: 10.1186/s13020-023-00863-0 -
World Journal of Diabetes Dec 2023Uncontrolled hyperglycemia or poorly managed disease increases the propensity for a number of diabetes-related complications targeting major organs including the heart,...
Uncontrolled hyperglycemia or poorly managed disease increases the propensity for a number of diabetes-related complications targeting major organs including the heart, eyes, and kidney. Although the mechanisms by which diabetes induces cardiovascular diseases include oxidative stress and inflammation, when insulin resistance remains the key to the pathogenesis, as implicated in the two reviews in this issue. This editorial mainly comments on the potential preventive application of glycyrrhetinic acid (or 18β-GA) in relation to diabetic nephropathy. The thera-peutic or preventive effects of 18β-GA, as a hydrolytic product of glycyrrhizic acid that is a component of licorice, have been appreciated in other disorders, but have received much less attention in relation to diabetic complications. A study in this issue has identified 18β-GA as a therapeutic for preventing diabetic nephropathy and provides evidence to support efficacy in cultured human renal tubule cells . Although it represents a pilot study, the observations support a new therapeutic approach that warrants further ex-ploration.
PubMed: 38222784
DOI: 10.4239/wjd.v14.i12.1717