Gambogic acid, a caged xanthone compound derived from Garcinia, has been proven to be an important substance basis for the pharmacological effects of the plant. In recent years, it has received continuous attention due to its broad and significant pharmacological activities. Modern pharmacological investigations have demonstrated that gambogic acid endows various therapeutic effects such as anti-inflammatory, antioxidant, and anti-tumor activities, as well as benefits in retinopathy, organ protection, anti-microbial infection, bone protection, and neuropathic pain relief. Nevertheless, there is currently a lack of systematic summary and integration of the pharmacological effects and mechanisms of gambogic acid, which is critical for advancing the clinical application of this natural product. In addition, current research has raised concerns about potential safety risks associated with gambogic acid, such as organ toxicity, developmental toxicity, and hemolysis. Given this, this paper systematically reviewed and summarized the pharmacological effects, mechanisms, and toxicological profiles of gambogic acid, aiming to provide reference and data support for its clinical translation.
Xanthones/toxicity* ; Humans ; Animals ; Drugs, Chinese Herbal/toxicity* ; Garcinia/chemistry*

OBJECTIVETo investigate mechanism of inhibition on the lipopolysaccharide induced chronic inflammation of mangiferin by the regulation of mitogen-activated protein kinase (MAPK) signaling pathway.

METHODSixty SD rats were randomly divided into normal control, model control, positive drug control (prednisone, 5 mg x kg(-10 x d(-1)) and mangiferin (200, 100, 50 mg x kg(-1) x d(-1)) group. The chronic inflammation models were established by intermittent injection of lipopolysaccharide via the tail vein. The leucocyte count was measured. The levels of serum tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and soluble intercellular adhesion molecule 1 (sICAM-1) were detected by enzyme-linked immunosorbent assay (ELISA). The reverse transcription-polymerase chain reaction (RT-PCR) was applied to evaluate the expressions of p38, ERK, JNK gene of leucocyte in MAPK signaling pathway.

RESULTCompared with the model control, not only the leucocyte count and the level of serum TNF-alpha, IL-6, sICAM-1 but also the expressions of ERK, JNK gene of leukocyte were markedly reduced in mangiferin (200 mg x kg(-1) x d(-1)) group (P < 0.05). However, there was no statistics significance for the expression of p38 gene between the model control and the mangiferin (200 mg x kg(-1) x d(-1)) group.

CONCLUSIONAs a possible mechanism, the regulation of mangiferin on the expressions of ERK, JNK gene of leukocyte in MAPK signaling pathway was involved in its great inhibition on the chronic inflammation induced by lipopolysaccharide.

Animals ; Chronic Disease ; Gene Expression ; Inflammation ; chemically induced ; drug therapy ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-6 ; blood ; Leukocyte Count ; Leukocytes ; metabolism ; Lipopolysaccharides ; toxicity ; MAP Kinase Signaling System ; drug effects ; genetics ; Male ; Mangifera ; chemistry ; Mitogen-Activated Protein Kinases ; genetics ; Models, Animal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood ; Xanthones ; pharmacology ; therapeutic use

OBJECTIVETo study the oral chronic toxicity of 97% isopropyl thioxanthone (97% ITX) in rats, determine the no-observed adverse effect levels (NOAEL).

METHODSFour groups of rats were fed with foodstuff containing 97% ITX in the dosage of 1000.0, 250.0, 62.5 mg/kg respectively for 2 years. The general behavior, body weight, food availability ect. were observed during the experiment. At the end of the experiment, blood and urine samples were collected for routine and biochemical assays. The internal organs were taken for calculating their organ coefficients and histopathological examinations.

RESULTSDuring the experimental period, no obvious abnormality were found in the experimental animals. The body weight and the total food availability rate in the high dosage group of male were lower than that of control (P < 0.05). Hematology examination showed that the quantity of Hb and RBC in high dosage groups of both the male and female and Hb in the male middle group were all lower than the control group (P < 0.01 or P < 0.05). Analysis of correlation indicated that r = -0.433, P < 0.01 in male, r = -0.337, P < 0.01 in female of Hb; r = -0.266, P < 0.05 in male, r = -0.317, P < 0.01 in female of RBC. There were obviously negative correlation. Serum biochemistry examination showed the concentration of CHO in the high and middle dosage treated rats of male and female were higher than that of the control (P < 0.01 or P < 0.05). Analysis of correlation indicated that r = 0.497, P < 0.01 in male, r = 0.417, P < 0.01 in female. No abnormality were found in urine examination. The organ weight and organ coefficient such as liver, were higher than control group (P < 0.01). The result of histopathological examinations displayed that the renal tubule Cast and the tubulointerstitial nephritis in the treated groups were higher than that of control group (P < 0.01).

CONCLUSION97% ITX could obviously interfere with the animals' physical condition, and reduce the number of RBC and the concentration of Hb in the blood, interact metabolism of lipoid and induce the concentration of CHO in the serum. The livers of the treated rats are compensatory enlarged. And kidneys of the poisoning animals are damaged. The 2 years oral NOAEL of 97% ITX in rats are more than 4.63 mg/kg for female rats, and larger than 4.06 mg/kg for male rats.

Administration, Oral ; Animals ; Female ; Male ; No-Observed-Adverse-Effect Level ; Rats ; Rats, Wistar ; Toxicity Tests, Chronic ; Xanthones ; toxicity

The involvement of mucosal mast cells (MMC) in the pathophysiology of irritable bowel syndrome (IBS) is still controversial. We aimed to re-evaluate the role of MMC in visceral hypersensitivity associated with IBS using a rat IBS model that develops the IBS symptom after a subsidence of acetic acid-induced colitis. No significant difference in the number of MMC was observed between normal rat colon and IBS rat colon. (61.7 +/-2.9/mm 2 in normal vs. 88.7 +/-13.3/mm 2 in IBS, p >0.29). However, the degranulation rate of MMC was significantly higher in IBS rat colon (49.5 +/-2.4% in normal vs. 68.8 +/-3.4% in IBS, p >0.05). Pretreatment of a mast cell stabilizer, doxantrazole (5 mg/kg, i.p.), reduced the degranulation rate of MMC and significantly attenuated visceral hypersensitivity to rectal distension in IBS rat, whereas it had no effect on the visceral sensory responses in normal rat. These results suggest that, although the number of MMC is not significantly changed in IBS rat colon, the higher degranulation rate of MMC is responsible for visceral hypersensitivity in this model IBS.
Acetic Acid/toxicity ; Animals ; Cell Count ; Colitis/chemically induced/*pathology ; Hypersensitivity/*pathology ; Image Processing, Computer-Assisted ; Intestinal Mucosa/*pathology ; Irritable Bowel Syndrome/*pathology ; Male ; Mast Cells/drug effects/*pathology ; Models, Theoretical ; Phosphodiesterase Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Thioxanthenes/pharmacology ; Viscera/immunology ; Xanthones/pharmacology