Combined Administration of Curcumin and Chondroitin Sulfate Alleviates Cartilage Injury and Inflammation via NF-κB Pathway in Knee Osteoarthritis Rats.

Objective: Osteoarthritis (OA) is a degenerative chronic disease that most often occurs in the knee joint. Studies have shown that some food supplements, such as curcumin and chondroitin sulfate, are effective in treating knee osteoarthritis (KOA) by exhibiting different protective effects. In this study, we further investigated the combined therapeutic effects of curcumin and chondroitin sulfate on cartilage injury in rats with arthritis. Methods: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. All rats were randomly divided into five groups: Ctrl (control), model (saline), Cur (20 mg/kg curcumin in saline), CS (100 mg/kg chondroitin sulfate in saline), and CA (20 mg/kg curcumin and 100 mg/kg chondroitin sulfate in saline); drugs were given 2 weeks after MIA injection. The histomorphological changes of cartilage were observed by safranin fast green staining, H&E staining, and micro-CT scanning. Also, the levels of PGE2, TNF-α and IL-1ß in the arthral fluid and serum were determined by the ELISA kits. The activities of SOD, CAT, COMP, MMP-3, and type II collagen were detected by biochemical kits. The expressions of TLR4, p-NF-κB, NF-κB, and COX-2 in cartilage were detected by Western blot. Results: Data show that serum levels of IL-1ß (p < 0.05), SOD (p < 0.0001), and MMP-3 (p < 0.001) were downregulated significantly in the CA group when compared to those in the model group. Meanwhile, obvious repair of cartilage with higher contains collagen II (p < 0.0001) could be observed in the CA group than the ones in Cur or CS group. In addition, significant downregulation of the expression of p-p65/p65 (p < 0.05) was found in the CA group. Conclusion: Our findings showed that combined administration of curcumin and chondroitin sulfate could exert better repair for KOA in rat models. This may hold great promise for discovering potential drugs to treat KOA and may improve treatment options for it.

Rosmarinic Acid Ameliorates H2O2-Induced Oxidative Stress in L02 Cells Through MAPK and Nrf2 Pathways.

Liver cells are easily damaged by oxidative stress during progression both in liver development and throughout adult life, resulting in tissue pathology that ranges from simple hepatitis to nonalcoholic fatty liver disease. In this study, we determined the attenuation of oxidative stress in liver cells with pretreatment of rosmarinic acid (RA), which is an antioxidant agent from Rosmarinus officinalis. The human liver cell line L02 was damaged by hydrogen peroxide (H2O2). In the RA treatment group, the viability of L02 cells increased and the intracellular reactive oxygen species levels decreased compared with the H2O2-induced damage group. Analysis of flow cytometry revealed that the percentage of G2/M cell cycle arrest and cell apoptosis decreased in the RA treatment group. This alteration was associated with activation of a G2/M DNA damage and oxidative stress apoptotic signal. Furthermore, we determined the redox-sensitive protein expression of mitogen-activated protein kinases (MAPKs), quinone acceptor oxidoreductase 1 (NQO1), and nuclear factor E2-related factor 2 (Nrf2), and the expression of both MAPKs and Nrf2 was activated in the RA group. Results showed that the relevant protein expression of MAPKs and Nrf2 was activated in the RA group. Thus, RA protected L02 cells from oxidative damage through suppressing cell cycle arrest and cell apoptosis with the activation of MAPK and Nrf2 signaling pathways.

Astragaloside exerts anti-photoaging effects in UVB-induced premature senescence of rat dermal fibroblasts through enhanced autophagy.

BACKGROUND: Astragalus membranaceus is a fundamental herb in Traditional Chinese Medicine and has attracted significant attention due to its anti-inflammatory, and longevity effects. However, its anti-photoaging property remains to be defined. Autophagy plays important roles in regulating cell homeostasis and aging processes. Whether regulation of autophagy could be an efficient way for anti-photoaging is still unclear. OBJECTIVE: To investigate the effects and the possible mechanism of astragaloside on anti-photoaging in UVB-induced photoaging cell model. METHODS: Primary rat dermal fibroblasts were prepared by repeated exposures to UVB irradiation. The expression levels of cytokines and signal molecules were determined by RT-PCR and western blot. SA-ß-gal staining was performed to indicate senescence level. Intracellular reactive oxygen species and mitochondrial membrane potential were monitored by fluorescent probes DCFH-DA and JC-1. The cell viability was determined using Cell Counting Kit-8. RESULTS: Astragaloside increases the expression of collagen-I (Col1) downregulated by UVB. UVB-induced oxidative stress and photoaging could be inhibited by astragaloside. The degradation of Col1 caused by UVB irradiation through activated ERK and p38 signals could be suppressed by astragaloside. Importantly, autophagy was induced by astragaloside. Col1 could be further accumulated by chloroquine but decreased by 3-methyladenine in photoaged cell after treatment of astragaloside. CONCLUSION: Autophagy play essential roles, at least partially, in modulating the formation and degradation of Col1 in photoaging cell model. Astragaloside increases the accumulation of Col1 and protects UVB-induced photoaging cells through not only ERK and p38 inhibition but also autophagy activation, indicating the potential application of astragaloside for anti-photoaging therapy.

Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues.

The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9-15) were evaluated against human lung adenocarcinoma (A549) and human prostate cancer (PC3) cells. This is the first evaluation of the cytotoxicities of these alkaloids in these cancer cell lines and it revealed that analogue 15 had comparable cytotoxic activity to its natural parent compound, (±)-hanishin (3). This study provides useful information for further structural modification of these alkaloids in order to develop novel antitumor agents.