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Phytotherapy Research : PTR Dec 2018In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the... (Review)
Review
In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the other hand, there is a growing demand by industry for plants used in traditional medicine that could be incorporated in foods, nutraceuticals, cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the Fabaceae family and has been recognized since ancient times for its ethnopharmacological values. This plant contains different phytocompounds, such as glycyrrhizin, 18β-glycyrrhetinic acid, glabrin A and B, and isoflavones, that have demonstrated various pharmacological activities. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, anti-inflammatory, antiviral, antioxidant, and antidiabetic activities. A few toxicological studies have reported some concerns. This review addresses all those issues and focuses on the pharmacological activities reported for G. glabra. Therefore, an updated, critical, and extensive overview on the current knowledge of G. glabra composition and biological activities is provided here in order to explore its therapeutic potential and future challenges to be utilized for the formulation of new products that will contribute to human well-being.
Topics: Animals; Anti-Bacterial Agents; Antioxidants; Antiviral Agents; Enzyme Inhibitors; Ethnopharmacology; Glycyrrhiza; Glycyrrhizic Acid; Humans; Hypoglycemic Agents; Medicine, Traditional; Phytochemicals; Plant Extracts
PubMed: 30117204
DOI: 10.1002/ptr.6178 -
Journal of the American Society of... Mar 2023Cells undergoing necrosis release extracellular high mobility group box (HMGB)-1, which triggers sterile inflammation upon AKI in mice. Neither deletion of HMGB1 from...
SIGNIFICANCE STATEMENT
Cells undergoing necrosis release extracellular high mobility group box (HMGB)-1, which triggers sterile inflammation upon AKI in mice. Neither deletion of HMGB1 from tubular epithelial cells, nor HMGB1 antagonism with small molecules, affects initial ischemic tubular necrosis and immediate GFR loss upon unilateral ischemia/reperfusion injury (IRI). On the contrary, tubular cell-specific HMGB1 deficiency, and even late-onset pharmacological HMGB1 inhibition, increased functional and structural recovery from AKI, indicating that intracellular HMGB1 partially counters the effects of extracellular HMGB1. In vitro studies indicate that intracellular HMGB1 decreases resilience of tubular cells from prolonged ischemic stress, as in unilateral IRI. Intracellular HMGB1 is a potential target to enhance kidney regeneration and to improve long-term prognosis in AKI.
BACKGROUND
Late diagnosis is a hurdle for treatment of AKI, but targeting AKI-CKD transition may improve outcomes. High mobility group box-1 (HMGB1) is a nuclear regulator of transcription and a driver of necroinflammation in AKI. We hypothesized that HMGB1 would also modulate AKI-CKD transition in other ways.
METHODS
We conducted single-cell transcriptome analysis of human and mouse AKI and mouse in vivo and in vitro studies with tubular cell-specific depletion of Hmgb1 and HMGB1 antagonists.
RESULTS
HMGB1 was ubiquitously expressed in kidney cells. Preemptive HMGB1 antagonism with glycyrrhizic acid (Gly) and ethyl pyruvate (EP) did not affect postischemic AKI but attenuated AKI-CKD transition in a model of persistent kidney hypoxia. Consistently, tubular Hmgb1 depletion in Pax8 rtTA, TetO Cre, Hmgb1fl/fl mice did not protect from AKI, but from AKI-CKD transition. In vitro studies confirmed that absence of HMGB1 or HMGB1 inhibition with Gly and EP does not affect ischemic necrosis of growth-arrested differentiated tubular cells but increased the resilience of cycling tubular cells that survived the acute injury to oxidative stress. This effect persisted when neutralizing extracellular HMGB1 with 2G7. Consistently, late-onset HMGB1 blockade with EP started after the peak of ischemic AKI in mice prevented AKI-CKD transition, even when 2G7 blocked extracellular HMGB1.
CONCLUSION
Treatment of AKI could become feasible when ( 1 ) focusing on long-term outcomes of AKI; ( 2 ) targeting AKI-CKD transition with drugs initiated after the AKI peak; and ( 3 ) targeting with drugs that block HMGB1 in intracellular and extracellular compartments.
Topics: Humans; Animals; Mice; HMGB1 Protein; Kidney; Regeneration; Epithelial Cells; Oxidative Stress; Glycyrrhizic Acid; Acute Kidney Injury; Renal Insufficiency, Chronic
PubMed: 36857499
DOI: 10.1681/ASN.0000000000000024 -
Ecotoxicology and Environmental Safety May 2023Deoxynivalenol (DON) can affect health and growth performance of pigs, resulting in significant economic losses in swine production. The aim of this study was to...
Deoxynivalenol (DON) can affect health and growth performance of pigs, resulting in significant economic losses in swine production. The aim of this study was to investigate the effect of glycyrrhizic acid combined with compound probiotics, i.e. Enterococcus faecalis plus Saccharomyces cerevisiae (GAP) on improving growth performance, intestinal health and its fecal microbiota composition change of piglets challenged with DON. A total of 160 42-day-old weaned piglets (Landrace × Large White) were used and the experimental period was 28 d. The results showed that supplementing GAP in the diet significantly improved the growth performance of piglets challenged with DON and alleviate DON-induced intestinal damage by reducing ALT, AST and LDH concentrations in serum, increasing the morphological parameters of jejunum, and decreasing DON residues in serum, liver and feces. Moreover, GAP could significantly decrease the expressions of inflammation and apoptosis genes and proteins (IL-8, IL-10, TNF-α, COX-2, Bax, Bcl-2 and Caspase 3), and increase the expressions of tight-junction proteins and nutrient transport factor genes and proteins (ZO-1, Occludin, Claudin-1, ASCT2 and PePT1). In addition, it was also found that GAP supplementation could significantly increase the diversity of gut microbiota, maintain microbial flora balance and promote piglet growth by significantly increasing the abundance of beneficial bacterium such as Lactobacillus and reducing the abundance of harmful bacterium such as Clostridium_sensu_stricto_1. In conclusion, GAP addition to piglet diets contaminated with DON could significantly promote the health and growth performance of piglets though alleviating DON-induced hazards. This study provided a theoretical basis for the application of GAP to alleviate DON toxicity for animals.
Topics: Swine; Animals; Glycyrrhizic Acid; Intestines; Trichothecenes; Probiotics
PubMed: 37054475
DOI: 10.1016/j.ecoenv.2023.114901 -
Oxidative Medicine and Cellular... 2022With unknown etiology and limited treatment options, neonatal hypoxic-ischemic brain damage (HIBD) remains a major cause of mortality in newborns. Ferroptosis, a...
With unknown etiology and limited treatment options, neonatal hypoxic-ischemic brain damage (HIBD) remains a major cause of mortality in newborns. Ferroptosis, a recently discovered type of cell death triggered by lipid peroxidation, is closely associated with HIBD. High-mobility group box 1 (HMGB1), a molecule associated with inflammation damage, can induce neuronal death in HIBD. However, it remains unknown whether HMGB1 contributes to neuronal ferroptosis in patients with HIBD. Herein, glycyrrhizin (GL), an HMGB1 inhibitor, was used to investigate the relationship between ferroptosis and HMGB1. RAS-selective lethal 3(RSL3), a ferroptosis agonist, was administered to further confirm the changes in the signaling pathway between HMGB1 and ferroptosis. Western blot analysis revealed that GL markedly suppressed the expression of HMGB1 and increased the level of GPX4 in the context of HIBD. We observed changes in neuronal ultrastructure via transmission electron microscopy to further confirm the occurrence of ferroptosis. Real-time PCR indicated that GL inhibited the expression of ferroptosis-related genes and inflammatory factors. Immunofluorescence and immunohistochemistry staining confirmed GL inhibition of neuronal damage and ferroptosis in HIBD associated with GPX4 and ROS. GL not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by HIBD in vivo. More importantly, GL may improve oxidative stress imbalance and mitochondrial damage, alleviate the downstream production of inflammatory factors, and ultimately reduce ferroptosis and damage to cortical neurons following HIBD via the HMGB1/GPX4 pathway. In conclusion, we showed for the first time that GL could suppress the occurrence of neuronal ferroptosis and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. These findings highlight the potential of HMGB1 signaling antagonists to treat neuronal damage by suppressing ferroptosis, provide new and unique insights into GL as a neuroprotective agent, and suggest new prevention and treatment strategies for HIBD.
Topics: Animals; Animals, Newborn; Brain; Ferroptosis; Glycyrrhizic Acid; HMGB1 Protein; Hypoxia-Ischemia, Brain; Neuroinflammatory Diseases; Phospholipid Hydroperoxide Glutathione Peroxidase; Rats
PubMed: 35432719
DOI: 10.1155/2022/8438528 -
International Journal of Molecular... Sep 2022Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, which is characterized by hyperglycemia, chronic insulin resistance, progressive decline in β-cell... (Review)
Review
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, which is characterized by hyperglycemia, chronic insulin resistance, progressive decline in β-cell function, and defect in insulin secretion. It has become one of the leading causes of death worldwide. At present, there is no cure for T2DM, but it can be treated, and blood glucose levels can be controlled. It has been reported that diabetic patients may suffer from the adverse effects of conventional medicine. Therefore, alternative therapy, such as traditional Chinese medicine (TCM), can be used to manage and treat diabetes. In this review, glycyrrhizic acid (GL) and its derivatives are suggested to be promising candidates for the treatment of T2DM and its complications. It is the principal bioactive constituent in licorice, one type of TCM. This review comprehensively summarized the therapeutic effects and related mechanisms of GL and its derivatives in managing blood glucose levels and treating T2DM and its complications. In addition, it also discusses existing clinical trials and highlights the research gap in clinical research. In summary, this review can provide a further understanding of GL and its derivatives in T2DM as well as its complications and recent progress in the development of potential drugs targeting T2DM.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycyrrhizic Acid; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin Secretion
PubMed: 36232291
DOI: 10.3390/ijms231910988 -
Russian Journal of Bioorganic Chemistry 2022Glycyrrhizic acid and its primary metabolite glycyrrhetinic acid, are the main active ingredients in the licorice roots (glycyrrhiza species), which are widely used in...
UNLABELLED
Glycyrrhizic acid and its primary metabolite glycyrrhetinic acid, are the main active ingredients in the licorice roots (glycyrrhiza species), which are widely used in several countries of the world, especially in east asian countries (China, Japan). These ingredients and their derivatives play an important role in treating many diseases, especially infectious diseases such as COVID-19 and hepatic infections. This review aims to summarize the different ways of synthesising the amide derivatives of glycyrrhizic acid and the main ways to synthesize the glycyrrhitinic acid derivatives. Also, to determine the main biological and pharmacological activity for these compounds from the previous studies to provide essential data to researchers for future studies.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1134/S1068162022050132.
PubMed: 35919388
DOI: 10.1134/S1068162022050132 -
Toxins Dec 2022Deoxynivalenol (DON) is a widespread mycotoxin that affects the intestinal health of animals and humans. In the present study, we performed RNA-sequencing and 16S rRNA...
Deoxynivalenol (DON) is a widespread mycotoxin that affects the intestinal health of animals and humans. In the present study, we performed RNA-sequencing and 16S rRNA sequencing in piglets after DON and glycyrrhizic acid and compound probiotics (GAP) supplementation to determine the changes in intestinal transcriptome and microbiota. Transcriptome results indicated that DON exposure altered intestinal gene expression involved in nutrient transport and metabolism. Genes related to lipid metabolism, such as PLIN1, PLIN4, ADIPOQ, and FABP4 in the intestine, were significantly decreased by DON exposure, while their expressions were significantly increased after GAP supplementation. KEGG enrichment analysis showed that GAP supplementation promoted intestinal digestion and absorption of proteins, fats, vitamins, and other nutrients. Results of gut microbiota composition showed that GAP supplementation significantly improved the diversity of gut microbiota. DON exposure significantly increased , , and abundances and decreased , , and abundances; however, dietary supplementation with GAP observably recovered their abundances to normal. In addition, predictive functions by PICRUSt analysis showed that DON exposure decreased lipid metabolism, whereas GAP supplementation increased immune system. This result demonstrated that dietary exposure to DON altered the intestinal gene expressions related to nutrient metabolism and induced disturbances of intestinal microbiota, while supplementing GAP to DON-contaminated diets could improve intestinal health for piglets.
Topics: Humans; Animals; Swine; Glycyrrhizic Acid; RNA, Ribosomal, 16S; Transcriptome; Intestines; Microbiota; Probiotics; Dietary Supplements
PubMed: 36548753
DOI: 10.3390/toxins14120856 -
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 -
Journal of Orthopaedic Surgery and... Feb 2021Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the...
BACKGROUND
Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the fact that OA can be triggered by multiple etiological factors, this disease is hard to be cured. Therefore, it is of great necessity for us to find novel targets or drugs for OA treatment.
MATERIALS AND METHODS
The chondrocytes were treated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce pyroptosis in OA. The cell proliferation was detected by Cell Counting Kit-8 assay (CCK-8 assay). Enzyme-linked immunosorbent assay (ELISA) was used for the detection of pyroptosis-related inflammatory factors. Then, the antagonists for gasdermin D (GSDMD) (disulfiram) and high mobility group box 1 (HMGB1) (glycyrrhizic acid) were used to treat the cell model to observe the effects of disulfiram and glycyrrhizic acid on the proliferation of chondrocytes in OA. The protein levels of pyroptosis-related inflammatory factors were measured by western blot, and the levels of aldehyde dehydrogenase (ALDH) and reactive oxygen species (ROS) were measured by corresponding commercial kits.
RESULTS
After chondrocytes were induced by LPS and ATP, the cell proliferation was decreased and the expressions of pyroptosis-related inflammatory factors were increased. Disulfiram and glycyrrhizic acid treatment led to enhanced cell proliferation and increased expressions of pyroptosis-related inflammatory factors, while disulfiram showed better alleviative effects on the inflammation in chondrocytes in OA. However, co-treatment with disulfiram at a high concentration and glycyrrhizic acid did not result in higher proliferation of chondrocytes and alleviated inflammation, but led to oxidative stress.
CONCLUSION
In conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA.
Topics: Cell Proliferation; Cells, Cultured; Chondrocytes; Disulfiram; Dose-Response Relationship, Drug; Glycyrrhizic Acid; Humans; Inflammation; Osteoarthritis; Phytotherapy; Pyroptosis
PubMed: 33579316
DOI: 10.1186/s13018-021-02262-3 -
ACS Applied Materials & Interfaces May 2021COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be...
COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Coronavirus Nucleocapsid Proteins; Cytokines; Female; Glycyrrhizic Acid; Humans; Inflammation; Liver; Lung; Mice; Mice, Inbred BALB C; Murine hepatitis virus; Nanoparticles; Phosphoproteins; RAW 264.7 Cells; SARS-CoV-2; THP-1 Cells; Viral Load; Virus Diseases; Virus Replication; COVID-19 Drug Treatment
PubMed: 33930273
DOI: 10.1021/acsami.1c02755