gambogic-acid and Inflammation

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of GA on inflammatory response of ARPE-19 cells remains unclear. In our study, ARPE-19 cells were stimulated by palmitic acid (PA) induction in the presence of 30 mM glucose and then treated with 0.5, 1, 2, 5, 10, or 20 μM GA. CCK-8 assay showed that cell viability was increased by GA treatment at doses of 0.5, 1, and 2 μM instead of higher doses. ELISA analysis found that GA dose-dependently reduced the production of pro-inflammatory mediators TNF-α and IL-1β. Western blot indicated that GA downregulated the expression of NLRP3 inflammasome components including TXNIP, NLRP3, ASC, cleaved-caspase-1, and cleaved-IL-1β in a dose-dependent manner. In addition, Western blot and immunofluorescence analysis suggested that GA effectively increased the protein level of nuclear factor E2-related factor-2 (Nrf2). RT-qPCR showed that GA significantly increased the mRNA levels of Heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase1 (NQO1). Furthermore, Nrf2 siRNA transfection confirmed the above effects of GA. In total, subtoxic doses of GA significantly flattened the inflammatory response induced by HG and PA in ARPE-19 cells via modulating the Nrf2 signaling pathway.

Topics: Cell Line; Diabetic Retinopathy; Humans; Inflammation; NF-E2-Related Factor 2; Palmitic Acid; Xanthones

Mastitis is one of the most common diseases among dairy cows. There is still much debate worldwide as to whether antibiotic therapy should be given to dairy cows, or if natural products should be taken as a substitute for antibacterial therapy. As the antibiotic treatment leads to the bacterial resistance and drug residue in milk, introducing natural products for mastitis is becoming a trend. This study investigates the mechanisms of the protective effects of the natural product gambogic acid (GA) in lipopolysaccharide (LPS)-induced mastitis. For in vitro treatments, it was found that GA reduced IL-6, TNF-α, and IL-1β levels by inhibiting the phosphorylation of proteins in the nuclear factor κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway. GA also maintained a stable membrane mitochondrial potential and inhibited the overproduction of reactive oxygen species, which protected the cells from apoptosis. On the other hand, in vivo treatments with GA were found to reduce pathological symptoms markedly, and protected the blood-milk barrier from damage induced by LPS. The results demonstrate that GA plays a vital role in suppressing inflammation, alleviating the apoptosis effect, and protecting the blood-milk barrier in mastitis induced by LPS. Thus, these results suggest that the natural product GA plays a potential role in mastitis treatment.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Caspase 3; Caspase 9; Cell Line; Cytokines; Disease Models, Animal; Epithelial Cells; Female; Inflammation; Lipopolysaccharides; Mammary Glands, Animal; MAP Kinase Signaling System; Mastitis; Membrane Potential, Mitochondrial; Mice; NF-kappa B p50 Subunit; Phosphorylation; Pregnancy; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Xanthones

Gamboge is the dry resin secreted by Garcinia hanbaryi Hook.f, with the function of promoting blood circulation and anti‑cancer effects, detoxification, hemostasis and killing insects. It is also used for the treatment of cancer, brain edema and other diseases. Gambogic acid is the main effective constituent of Gamboge. The present study tested the hypothesis that the effect of Gambogic acid prevents angiotensin II‑induced abdominal aortic aneurysm (AAA), and explored its underlying mechanism. It was demonstrated that gambogic acid significantly inhibited AAA incidence rate, and reduced edge leading aortic diameter and aortic wall thickness in AAA mice. Gambogic acid treatment markedly decreased the levels of proinflammatory cytokines and oxidative stress factors, and transforming growth factor‑β (TGF‑β) and matrix metalloproteinase (MMP)‑2 and MMP‑9 protein expression in AAA mice. Furthermore, Gambogic acid decreased expression of phosphatidylinositol 3‑kinase (PI3K), and phosphorylation of protein kinase B (Akt), mechanistic target of rapamycin (mTOR) and p70‑S6 kinase 1. It also suppressed nuclear factor (NF)‑κB protein expression in AAA mice. The findings of the present study indicated that Gambogic acid prevents angiotensin II‑induced AAA through inflammatory and oxidative stress‑dependent targeting of the PI3K/Akt/mTOR and NF‑κB signaling pathways.

Topics: Angiotensin II; Animals; Aortic Aneurysm, Abdominal; Garcinia; Inflammation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Xanthones

Gamboge is the dried resin secreted by the Garcinia maingayi gambogic tree and is a substance that may be used to treat a variety of diseases, exhibits anti‑tumor and detoxification effects and prevents bleeding. The primary active constituent is gambogic acid. The present study aimed to investigate the anti‑inflammatory effects of gambogic acid in rheumatoid arthritis (RA) rats and to elucidate the mechanisms by which these effects occur. The swelling degree, the clinical arthritic scoring and pain threshold measurements were used to evaluate the effects of gambogic acid on RA. ELISA kits and western blot analysis were used to investigate inflammatory processes and the expression of RA‑associated proteins, respectively. The present results demonstrated that gambogic acid significantly inhibited the degree of right foot swelling, increased pain thresholds and reduced clinical arthritic scores of RA rats. Treatment with gambogic acid suppressed the activities of interleukin (IL)‑1β and IL‑6, promoted the protein expression of phosphorylated (p)‑Akt serine/threonine kinase (Akt), p‑mammalian target protein of rapamycin (mTOR) and inhibited hypoxia‑inducible factor‑1α and vascular endothelial growth factor expression in RA rats. The results of the present study therefore suggest that the anti‑inflammatory effects of gambogic acid in RA rats occur via regulation of the phosphoinositide 3‑kinase/Akt/mTOR signaling pathway.

Topics: Animals; Arthritis, Rheumatoid; Disease Models, Animal; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Interleukin-1beta; Interleukin-6; Male; Pain Threshold; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A; Xanthones

We have previously reported a continuous activation of caspase-1 and increased interleukin (IL)-1β levels in early rheumatoid arthritis (RA). These observations raised the hypothesis that drugs targeting the IL-1β pathway, in addition to tumour necrosis factor (TNF), may be particularly effective for early RA treatment. We have recently identified gambogic acid as a promising therapeutic candidate to simultaneously block IL-1β and TNF secretion. Our main goal here was to investigate whether gambogic acid administration was able to attenuate inflammation in antigen-induced arthritis (AIA) rats.. Gambogic acid was administered to AIA rats in the early and late phases of arthritis. The inflammatory score, ankle perimeter, and body weight were evaluated during the period of treatment. Rats were sacrificed after 19 days of disease progression and paw samples were collected for histological and immunohistochemical evaluation.. We found that inflammation in joints was significantly suppressed following gambogic acid administration. Histological and immunohistochemical evaluation of treated rats revealed normal joint structures with complete abrogation of the inflammatory infiltrate and cellular proliferation.. Our results suggest that gambogic acid has significant anti-inflammatory properties and can possibly constitute a prototype anti-inflammatory drug with therapeutic efficacy in the treatment of inflammatory diseases such as RA.

Topics: Animals; Anti-Inflammatory Agents; Antigens; Arthritis, Experimental; Caspase 1; Cell Proliferation; Disease Models, Animal; Disease Progression; Female; Inflammation; Interleukin-1beta; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Xanthones

Psoriasis is a chronic T cell-mediated inflammatory skin disease. Studies have shown that angiogenesis plays an important role in the pathogenesis of psoriasis. Studies have also indicated that Gambogic acid (GA) inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis therapies.. The aim of this study was to investigate the anti-psoriatic effect of GA and the possible mechanisms.. MTT test on HaCaT cells and immunofluorescence on HUVEC cells were processed. An O/W cream of GA was prepared and topically applied to the ears of K14-VEGF transgenic mice and psoriasis-like guinea-pigs, and the tail skin of Balb/C mice independently. Furthermore, hematoxylin-eosin staining of tissues from three models and immunohistochemistry staining of ear samples from K14-VEGF mice were performed.. In vitro, GA inhibited proliferation of HaCaTs and TNF-α-induced activation of NF-κB in HUVECs. In vivo, animals treated with GA showed significant morphological and histological improvements. Immunohistochemical analysis of K14-VEGF transgenic mice revealed that hyperplastic and inflamed vessels were suppressed with GA treatment. The expression of adhesion molecules such as ICAM-1 and E-selectin was significantly decreased. GA inhibited angiogenesis and the expression of VEGFR2 and p-VEGFR2. T lymphocyte infiltration and the expression of IL-17 and IL-22 were also reduced by GA treatment.. Our results suggest that GA has anti-psoriatic efficacy through inhibition of angiogenesis and inflammation. Therefore, GA is attractive and offers future potential for application in patients with psoriasis.

Topics: Animals; Cell Line; Disease Models, Animal; Drug Evaluation, Preclinical; Garcinia; Guinea Pigs; Human Umbilical Vein Endothelial Cells; Humans; Hyperplasia; Inflammation; Mice, Transgenic; Neovascularization, Pathologic; NF-kappa B; Phytotherapy; Plant Extracts; Plants, Medicinal; Psoriasis; Random Allocation; Skin; T-Lymphocytes; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Xanthones