Effect and mechanisms of Gambi-jung against high-fat diet-induced cardiac apoptosis in mice.

Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Ephedra sinica Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of uncoupling protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, optic atrophy protein 1, and fission protein 1. Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration.

New fusidane-type nortriterpenoids from the Arctic marine-derived fungus Simplicillium lamellicola culture medium with their inhibitory effect on benign prostatic hyperplasia.

Three new fusidane-type nortriterpenoids, simplifusinolide A, 24-epi simplifusinolide A, and simplifusidic acid L (1-3), were isolated from the EtOAc extract of the Arctic marine-derived fungus Simplicillium lamellicola culture medium, together with fusidic acid (4) and 16-O-deacetylfusicid acid (5). The structures of the isolated compounds were elucidated by NMR and MS analyses. The absolute configurations of compounds 1-3 were established by the quantum mechanical calculations of electronic circular dichroism and gauge-including atomic orbital NMR chemical shifts, followed by DP4 + analysis. Benign prostatic hyperplasia (BPH) is a major urological disorder in men worldwide. The anti-BPH potentials of the isolated compounds were evaluated using BPH-1 and WPMY-1 cells. Treatment with simplifusidic acid L (3) and fusidic acid (4) significantly downregulated the mRNA levels of the androgen receptor (AR) and its downstream effectors, inhibiting the proliferation of BPH-1 cells. Specifically, treatment with 24-epi simplifusinolide A (2) significantly suppressed the cell proliferation of both BPH-1 and DHT-stimulated WPMY-1 cells by inhibiting AR signaling. These results suggest the potential of 24-epi simplifusinolide A (2), simplifusidic acid L (3) and fusidic acid (4) as alternative agents for BPH treatment by targeting AR signaling.

Drynaria rhizome water extract alleviates high­fat diet­induced obesity in mice.

Drynaria rhizome is a herbal medicine used for strengthening bones and treating bone diseases in East Asia. Although obesity is considered to benefit bone formation, it has been revealed that visceral fat accumulation can promote osteoporosis. Given the complex relationship between bone metabolism and obesity, bone­strengthening medicines should be evaluated while considering the effects of obesity. The present study investigated the effects of Drynaria rhizome extract (DRE) on high­fat diet (HFD)­induced obese mice. DRE was supplemented with the HFD. Body weight, food intake, the expression levels of lipogenesis transcription factors, including sterol regulatory element binding protein (SREBP)­1, peroxisome proliferator­activated receptor (PPAR)­Î³ and adenosine monophosphate­activated protein kinase (AMPK)­α, and AMPK activation were evaluated. Mice fed DRE and a HFD exhibited reduced body weight without differences in food intake compared with those in the HFD group. Furthermore, DRE; upregulated AMPK­α of epididymal one; down­regulated SREBP­1 and PPAR­Î³, as determined using western blotting and quantitative polymerase chain reaction, respectively. Decreased lipid accumulation were observed in both fat pad and liver of HFD­fed mice, which were suppressed by DRE treatment. These results demonstrated the potential of DRE as a dietary natural product for strengthening bones and managing obesity.