Garcinia dulcis Extract Alleviates Inflammation in Kidney and Liver of the 2-Kidney-1-Clip Hypertensive rat.

Garcinia dulcis (GD) extract possesses anti-hypertensive property that are poorly characterized. This study aimed to investigate an anti-inflammatory effect of GD flower extract in the 2-kidney-1-clip (2K1C) hypertensive compared to sham operative (SO) rat. Male Wistar rats were divided into 2 groups; the 2K1C group in which a silver clip was placed around renal artery to induce hypertension, and the SO normotensive group. Four weeks later, each group of rats were further divided into 2 subgroups, each subgroup was orally gavaged of either corn oil (vehicle) or 50 mg/kg BW GD extract daily for 4 weeks. The malondialdehyde (MDA) levels in serum, liver, and kidney were determined. Hematoxylin and eosin staining was carried out for histological examination, Periodic acid - Schiff staining for glomerular injury, Masson's trichrome staining for renal fibrosis, and immunohistochemistry for either tumor necrosis factor alpha (TNF-α) or endothelial nitric oxide synthase (eNOS) investigation. Taken together, our results demonstrated that GD flower extract decreased the MDA level in both serum and liver and kidney tissue and suppressed the expression of TNF-α in both liver and kidney of 2K1C hypertensive rats. Mesangial cell proliferation, expansion of mesangial matrix, widening Bowman's capsule space, congestion of glomerular capillary and vessel, cloudy swelling of renal tubular epithelial cell, and renal fibrosis were observed in the kidneys of 2K1C rats. Therefore, we concluded that GD flower extract can alleviate liver and kidney inflammation in which partially attenuates the glomerular injury in the 2K1C rat.

Anti-Inflammatory Effect of Garcinol Extracted from Garcinia dulcis via Modulating NF-κB Signaling Pathway.

Garcinia is a significant medicinal plant with many beneficial phytoconstituents, including garcinol. This study investigated the anti-inflammatory effect of garcinol isolated from Garcinia dulcis fruit in LPS-activated THP-1 and Raw 264.7 macrophages. The results demonstrated that the low concentration of garcinol did not alter cell viability. Furthermore, co-incubation of garcinol with LPS inhibited the production of pro-inflammatory cytokines, including TNF-α, IL-8, IL-6, IL-1ß, and pro-inflammatory mediators, including iNOS and COX-2 at the mRNA and protein expression levels. Garcinol also decreased the secretion of TNF-α, IL-6, IL-1ß, PGE2, and NO. Moreover, the anti-inflammatory effects involved an alteration in the NF-κB signaling pathway. Downregulation of pIKKα/ß, pIκBα, and pNF-κB was observed, hence reducing the translocation of pNF-κB from the cytosol into the nucleus, which subsequently decreased the production of pro-inflammatory molecules. Therefore, garcinol isolated from Garcinia dulcis is a potential candidate as an anti-inflammatory agent for inflammation-related disease treatment.

Garcinia dulcis Flower Extract Alters Gut Microbiota and Fecal Metabolomic Profiles of 2K1C Hypertensive Rats.

Garcinia dulcis (GD) extract has been found to have anti-hypertensive properties in animal studies. GD can also alter the colonic microbiota of rats. However, the effects of GD on changes in the gut microbiota and metabolomic profiles of normotensive and hypertensive rats are currently unknown. The purpose of this study was to evaluate changes in the gut microbiota and metabolomic profiles of 2-kidneys-1 clip (2K1C) hypertensive rats after feeding with GD flower extract. Rats were randomly divided into the following 4 groups: sham operation (SO) receiving corn oil (CO) (SO + CO), SO receiving GD (SO + GD), 2K1C receiving corn oil (2K1C + CO) and 2K1C receiving GD (2K1C + GD). Body weight (BW) and systolic blood pressure (SBP) were measured weekly throughout the study. Gut microbiota and fecal metabolites were measured from fresh fecal contents. Alpha diversity results demonstrated a similar microbial richness and diversity between groups. Linear discriminant analysis (LDA) effect size (LEfSe) suggested that GD treatment affected gut microbial community structure in both hypertensive and normotensive rats. Feeding rats with GD caused metabolic alterations that rendered 2K1C + GD rats similar to SO + CO and SO + GD rats. Findings suggest that the impact of GD on gut microbiota and metabolite profiles may be related to its anti-hypertensive properties.

Camboginol and Morelloflavone from Garcinia dulcis (Roxb.) Kurz Flower Extract Promote Autophagic Cell Death against Human Glioblastoma Cells through Endoplasmic Reticulum Stress.

Garcinia dulcis is a tropical plant native to Southeast Asia that is traditionally used as a folk remedy to cure several pathological symptoms. Camboginol and morelloflavone have been revealed by previous studies as the principal bioactive compounds from the flower extract of G. dulcis. The disease-preventing properties of camboginol or morelloflavone, including anti-cancer, from various parts of G. dulcis have been revealed by recent studies. Glioblastoma is the aggressive malignant stage of brain cancer and suffers from chemotherapeutic resistance. This study aimed to test the anti-cancer effect of G. dulcis flower extract against the proliferation of A172 human glioblastoma cells. The extract had cytotoxic activity and promoted cell cycle arrest at the S and G2/M phases. Autophagic cell death was promoted by cytotoxic concentrations of the extract, as observed by enhancing autophagic flux and the expression of autophagic markers. Autophagic cell death induced by the extract might be associated with endoplasmic reticulum (ER) stress. Conclusively, it was indicated by this study that the extract from the flower of G. dulcis had a protective effect against the proliferation of A172 human glioblastoma cells through the induction of ER stress-mediated cytotoxic autophagy.

Suppression of Cholangiocarcinoma Cell Growth and Proliferation by Atractylodes lancea (Thunb) DC. through ERK-Signaling Cascade.

OBJECTIVE: The study aimed to investigate the inhibitory effects of AL on the ERK signaling molecules (ERK, p-ERK, cyclin D, and eIF4B) and the growth and proliferation of CCA cells. MATERIALS AND METHODS: The viability of the three CCA cell lines CL-6, HuCCT1, and HuH28 was determined using MTT assay. The effect of Ras/ERK inhibitors on protein expression in the presence of AL extract was investigated. The protein extracted from each CCA cell following exposure to AL and/or Ras/ERK inhibitors were separated on 12.5% SDS-PAGE. The analysis of mRNA expression following 48 and 72 hours of AL exposure in comparison with 0 hours (non-exposed cells) was performed by using RT-PCR. RESULTS: The potency of cytotoxic activity of AL (by MTT assay) was about three times higher than the standard drug 5-fluorouracil. The IC50 (concentration that inhibits cell growth by 50%) of AL for the CL-6, HuCCT-1 and HuH28 cell lines were 29.77±6.64, 35.45±4.96, and 35.32±6.69 µg/mL (mean+SD), respectively. The cells were exposed to AL extract at the IC50 for 0, 12, 24, 48, and 72 hours in the absence and presence of Ras/ERK inhibitors (salirasib and XMD8-92). Protein expression was determined by Western blot analysis. The results suggested the lack of significant inhibitory effect of AL on ERK at 48 and 72 hours of exposure in all CCA cell types. On the other hand, a significant inhibitory effect was observed with p-ERK expression in all CCA cell types. Cyclin D was significantly down-regulated at 72 hours of exposure in all cell types with different potencies. The expression of eIF4B was markedly inhibited in HuCCT-1 but slightly inhibited in CL-6 and HuH28 cells. Real-time PCR analysis revealed significant down-regulation of ERK following 72 hours of AL exposure in the HuCCT1 and HuH28, but not CL-6 cell. CONCLUSION: The ERK signaling cascade and downstream molecules are potential targets of action of AL in CCA.