Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. zhuchuanlong@jsph.org.cn.
Adolescent ; Child ; Female ; Glycyrrhizic Acid ; therapeutic use ; Humans ; Male ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Tablets

OBJECTIVETo systematically evaluate the efficacy and safety of diammonium glycyrrhizinate enteric-coated capsules versus diammonium glycyrrihizinate in patients with chronic viral hepatitis.

METHODSThe Chinese Biomedical Literature Database (CBM on CD-ROM) and the China Academic Journals Full-Text Database (Chinese National Knowledge Infrastructure, CNKI) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of diammonium glycyrrhizinate entetic-coated capsules versus diammonium glycyrrihizinate in treatment (less than 2 months) of chronic viral hepatitis published between 2005 and 2012. A meta-analysis was performed on the selected RCTs to determine the effects on alanine aminotransferase (ALT) normalization, serum levels of ALT, aspartate aminotransferase (AST), total bilirubin (TBil) and albumin, as well as rates of adverse reactions.

RESULTSNine RCTs, involving 687 patients, were included in the meta-analysis. Compared to the patients treated with diammonium glycyrrihizinate, the patient treated with diammonium glycyrrhizinate enteric-coated capsules had a significantly better recovery rate of ALT (relative risk (RR) =4.15, 95% confidence interval (CI):1.55 to 11.15, P less than 0.01) and significantly more robust decreases in ALT (weighted mean difference (WMD) = -32.75, 95% CI:-46.67 to-18.83, P less than 0.01) and AST (WMD = -12.70, 95% CI:-21.13 to-4.27, P less than 0.01). In contrast, the patients treated with diammonium glycyrrihizinate showed more robust improvements in the TBil level (WMD = -0.74, 95% CI:3.98 to 2.49, P =0.653) and albumin (WMD =1.03, 95% CI:-1.03 to 3.09, P =0.326), but the differences did not reach the threshold for statistical significance (P less than 0.05). Only four adverse reactions were reported, all of which were related to the lipid complex nature of the diammonium glycyrrhizin enteric-coated capsules and were mild, including dry mouth, dizziness and mild gastrointestinal discomfort and reactions.

CONCLUSIONDiammonium glycyrrhizinate enteric-coated capsules elicited superior anti-inflammatory and liver protection effects than diammonium glycyrrihizinate, and produced only mild side effects that are tolerable to the patients.

Capsules ; Glycyrrhizic Acid ; administration & dosage ; therapeutic use ; Hepatitis, Chronic ; drug therapy ; Hepatitis, Viral, Human ; drug therapy ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVETo investigate the neuroprotective effects of glycyrrhizin (Gly) as well as its effect on expression of high-mobility group box 1 (HMGB1) in rats after traumatic brain injury (TBI).

METHODSMale Sprague-Dawley rats were randomly divided into three groups: sham group, TBI group, and TBI+Gly group (n=36 per group). Rat TBI model was made by using the modified Feeney's method. In TBI+Gly group, Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB1/HMGB1 receptors including toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nuclear factor-κB(NF-κB) signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB1, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed.

RESULTSBeam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile, the over-expressions of HMGB1/HMGB1 receptors (TLR4 and RAGE)/NF-κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB1, RAGE and TLR4-positive cells and apoptotic cells were respectively 58.37% ± 5.06%, 54.15% ± 4.65%, 65.50% ± 4.83%, 52.02% ± 4.63% in TBI group and 39.99% ± 4.99%, 34.87% ± 5.02%, 43.33% ± 4.54%, 37.84% ± 5.16% in TBI+Gly group (all P<0.01 compared with TBI group).

CONCLUSIONGly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB1/HMGB1 receptors (TLR4 and RAGE)/NF-κB-mediated inflammatory responses in the injured rat brain.

Animals ; Brain Injuries ; drug therapy ; Glycyrrhizic Acid ; pharmacology ; therapeutic use ; HMGB1 Protein ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley

Viral hepatitis is clinical multiple strong infectious disease, to know characteristics of traditional Chinese medicine and western medicine clinical use in patients with viral hepatitis, the research object of this study is 41 180 cases of hospitalized patients with viral hepatitis in hospital information system from 17 grade A hospitals, using frequency statistics and association rules method to analyze the traditional Chinese medicine and western medicine clinical use information, the drug kinds analysis results: western medicine of reduced glutathione tablets use frequency is highest, 14 079 cases (34.61%), traditional Chinese medicine of diammonium glycyrrhizinateuse frequency is highest, 14 058 cases (34.56%); traditional Chinese medicine and western medicine drug combination in diammonium glycyrrhizinate combined with reduced glutathione tabletsuse frequency is highest, 8 607 cases (25.09%). The mechanism of drug classification results :both traditional Chinese medicine and western medicine are the sort of educed enzyme medicine that has the highest percentage of drug use, traditional Chinese medicine 10 983 cases (27.01%), western medicine, 9 595 cases (23.59%); traditional Chinese medicine and western medicine combination in a kind of medicine to clear heat and promote diuresis combined with educed enzyme drug use frequency is highest, 5 621 cases (13.82%). Through the analysis above, combine traditional Chinese and western medicine therapy for the treatment of viral hepatitis should be given priority. Traditional Chinese medicine to clear heat and promote diuresis combined with western medicine of educed enzyme drug is the most commonly appear in clinical two drug combination scheme, traditional Chinese medicine to clear heat and promote diuresis combined with western medicine of educed enzyme drug and nucleustide analogsis the most commonly appear in clinical three drug combination scheme.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glutathione ; therapeutic use ; Glycyrrhizic Acid ; therapeutic use ; Hepatitis, Viral, Human ; diagnosis ; drug therapy ; Hospital Information Systems ; Humans ; Infant ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Young Adult

OBJECTIVETo study the characteristics and regular pattern of the medicine in common use and combined medication in patients of acute pancreatitis in real world.

METHODCollect the information of 5 433 acute pancreatitis patients in 19 grade IIIA general hospitals in China, analysis by descriptive statistics and association rule.

RESULTIn the 5 433 patients of acute pancreatitis, the glycyrrhizic acid injection and somatostatin are the frequency top used Chinese traditional and western medication. Glycyrrhizic acid injection, somatostatin and insulin are the frequency top used drug combination pattern.

CONCLUSIONThe Chinese and western integrative medicine drug use pattern are accord with the clinical guideline of acute panceatitis. The hepatic and renal function, blood routine and coagulation function should be monitored when the medicines are used.

Adolescent ; Adult ; Aged ; Anti-Inflammatory Agents ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycyrrhizic Acid ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Pancreatitis ; drug therapy ; Somatostatin ; therapeutic use ; Young Adult

Viral hepatitis was the most common infectious disease in china. But the diagnosis and treatment were varied because the viral hepatitis patients were hospitalized in different kinds of hospital such as infectious disease hospital, general hospital and Chinese medical hospital. It was necessary to know clinical characters and information of viral hepatitis patients in different hospitals. The general information, subtype distribution, prognosis, complication, medication and relations of onset with solar term from 41 180 viral hepatitis patients based on HIS data were analyzed. It was found that the age of patients between 18 to 59 years old was most; most patients were males. The national basic medical insurance was the most type of payment. The outcome of viral hepatitis in the youth and female were better than that in the old and male. Acute hepatitis was easer to restore than chronic hepatitis. Liver cirrhosis and hepatocellular carcinoma were the two most complications. The peak of onset was during summer solstice, slight heat and great heat. The most common Chinese medicine was Diammonium glycyrrhizinate and the most common western medicine was reduced glutathione. The combination of D. glycyrrhizinate with reduced glutathione, polyene phosphatidylcholine and thymosin was the main pattern. But It was not knew if the combination of western and Chinese medicine was the most effective therapy to protect liver function. It was necessary to take deeply research of the relationship between the combination therapy and their effectiveness.
Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Female ; Glutathione ; therapeutic use ; Glycyrrhizic Acid ; therapeutic use ; Hepatitis, Viral, Human ; drug therapy ; Hospitals ; Humans ; Male ; Middle Aged ; Young Adult

The aim of this study was to observe the protective effect of ademetionine 1, 4-butanedisulfonate on liver injury caused by chemotherapy in patients with leukemia. The clinical data of protective effect were analyzed retrospectively from January 2010 to April 2012. A total of 62 acute leukemia patients were divided into A group (27 cases) and B group (35 cases), the polyene phosphatidyl choline combined with ademetionine or combined with compound glycyrrhizin were given in A and B group, respectively. The changes of liver function were observed after 2 weeks, 5 patients in B group suffered from acute liver injury were treated by ademetionine as rescue therapy. Liver function was compared before and after treatment. The results showed that ALT and AST levels were significantly reduced in A group (P < 0.05), none of the patients (0/27) suffered from acute liver injury, but 14.29% (5/35) patients in B group suffered from acute liver injury, and liver function could be recovered by substitution treatment of ademetionine (the median time is 8 days, 5-14 days). It is concluded that the protective and therapeutic effect of ademetionine against liver injury caused by chemotherapy in patients with leukemia is better than that of compound glycyrrhizin.
Adult ; Antineoplastic Agents ; adverse effects ; Chemical and Drug Induced Liver Injury ; prevention & control ; Female ; Glycyrrhizic Acid ; therapeutic use ; Humans ; Leukemia ; drug therapy ; Male ; Middle Aged ; S-Adenosylmethionine ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo observe the efficacy and safety of total glucosides of paeony capsule (TGPC) in patients with mild and moderate alopecia areata.

METHODSA total of 86 outpatients were randomly allocated into two groups of TGPC (treatment, 44 cases) and compound glycyrrhizin tablet (control, 42 cases). The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B(2) and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets (CD3(+)CD4(+), CD3(+)CD8(+), Th, Ts, Th/Ts) of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction.

RESULTSIn the treatment group, the cured and markedly effective rate was 36.36% (16/44), 50.00% (22/44) and 68.18% (30/44) at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% (6/44). In the control group, the cured and markedly effective rate was 38.10% (16/42), 57.14% (24/42) and 71.43% (30/42), respectively, and the incidence rate of adverse reaction was 16.67% (7/42). The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups (P>0.05). TGPC and compound glycyrrhizin tablet can inhibit CD3(+)CD4(+) and CD3(+)CD8(+), and decrease the ratio of Th/Ts (P<0.05).

CONCLUSIONTGPC is effective and safe in the treatment of alopecia areata.

Adult ; Alopecia Areata ; drug therapy ; immunology ; Capsules ; Female ; Glucosides ; adverse effects ; therapeutic use ; Glycyrrhizic Acid ; adverse effects ; therapeutic use ; Humans ; Lymphocyte Subsets ; immunology ; Male ; Middle Aged ; Paeonia ; chemistry ; T-Lymphocytes ; immunology ; Tablets ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the role of p38MAPK pathway in the protective effect of glycyrrhiznatis against myocardial ischemia-reperfusion in rabbits.

METHODSThirty rabbits were randomly divided into control group, I/R group, and glycyrrhiznatis group. In the latter two groups, the left anterior descending branch of the coronary artery was ligated for 40 min followed by 120 min of reperfusion, and in glycyrrhiznatis group, glycyrrhiznatis was given intravenously at 2.5 mg/kg before the occlusion. Blood samples were taken to measure the plasma levels of TNF-alpha, IL-6, and IL-8 at 20 min before (T(0)) and 20 min (T(1)) and 40 min (T(2)) after the occlusion, and at 1 h (T(3)) and 2 h (T(4)) after the reperfusion. At the end of the reperfusion, the infarct size and the area at risk were defined by Evams and TTC staining. The heart was harvested and the levels of the p38 MAPK measured by Western blotting. The ultrastructures of the cardiac myocytes were observed under electron microscope.

RESULTSThe p38MAPK activity and the plasma levels of the inflammatory factors were significantly lower in gtycyrrhiznatis group than in I/R group (P<0.05). Glycgrrhiznatis significantly reduced the infarct size as compared with that in I/R group.

CONCLUSIONSlycyrrhiznatis can reduce myocardial ischemia-reperfusion injury by inhibiting p38MAPK activity and modulating the cytokine expression.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Cytokines ; metabolism ; Female ; Glycyrrhizic Acid ; therapeutic use ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; metabolism ; Rabbits ; Random Allocation ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism